bluuebunny/crossref_metadata_2025 huggingface dataset:
The bouquet of grapevine (Vitis viniferaL. cv. Cabernet Sauvignon) flowers arises from the biosynthesis of sesquiterpene volatiles in pollen grains
Authors: Martin Diane M. , Toub Omid , Chiang Angela , Lo Bernard C. , Ohse Sebastian , Lund Steven T. , Bohlmann Jörg
Published: April 2009

Terpenoid volatiles are important information molecules that enable pollinators to locate flowers and may protect reproductive tissues against pathogens or herbivores. Inflorescences of grapevine (Vitis viniferaL.) are composed of tiny green flowers that produce an abundance of sesquiterpenoid volatiles. We demonstrate that male flower parts of grapevines are responsible for sesquiterpenoid floral scent formation. We describe temporal and spatial patterns of biosynthesis and release of floral volatiles throughout the blooming ofV. viniferaL. cv. Cabernet Sauvignon. The biosynthesis of sesquiterpene volatiles, which are emitted with a light-dependent diurnal pattern early in the morning at prebloom and bloom, is localized to anthers and, more specifically, within the developing pollen grains. Valencene synthase (VvValCS) enzyme activity, which produces the major sesquiterpene volatiles of grapevine flowers, is present in anthers.VvValCStranscripts are most abundant in flowers at prebloom stages. Western blot analysis identified VvValCS protein in anthers, and in situ immunolabeling located VvValCS protein in pollen grains during bloom. Histochemical staining, as well as immunolabeling analysis by fluorescent microscopy and transmission electron microscopy, indicated that VvValCS localizes close to lipid bodies within the maturing microspore.
Quantitative magnetic resonance and optical imaging biomarkers of melanoma metastatic potential
Authors: Li Lin Z. , Zhou Rong , Xu He N. , Moon Lily , Zhong Tuoxiu , Kim Eun Ju , Qiao Hui , Reddy Ravinder , Leeper Dennis , Chance Britton , Glickson Jerry D.
Published: April 2009

Noninvasive or minimally invasive prediction of tumor metastatic potential would facilitate individualized cancer management. Studies were performed on a panel of human melanoma xenografts that spanned the full range of metastatic potential measured by an in vivo lung colony assay and an in vitro membrane invasion culture system. Three imaging methods potentially transferable to the clinic [dynamic contrast-enhanced (DCE) MRI,
T

1
ρ

-MRI, and low-temperature fluorescence imaging (measurable on biopsy specimens)] distinguished between relatively less metastatic and more metastatic human melanoma xenografts in nude mice. DCE-MRI, analyzed with the shutter-speed relaxometric algorithm and using an arterial input function simultaneously measured in the left ventricle of the mouse heart, yielded a blood transfer rate constant,
K
trans
, that measures vascular perfusion/permeability.
K
trans
was significantly higher in the core of the least metastatic melanoma (A375P) than in the core of the most metastatic melanoma (C8161). C8161 melanoma had more blood vascular structures but fewer functional blood vessels than A375P melanoma. The A375P melanoma exhibited mean
T

1
ρ

values that were significantly higher than those of C8161 melanoma. Measurements of
T
1
and
T
2
relaxation times did not differ significantly between these 2 melanomas. The mitochondrial redox ratio, Fp/(Fp + NADH), where Fp and NADH are the fluorescences of oxidized flavoproteins and reduced pyridine nucleotides, respectively, varied linearly with the in vitro invasive potential of the 5 melanoma cell lines (A375P, A375M, A375P10, A375P5, and C8161). This study shows that a harsh microenvironment may promote melanoma metastasis and provides potential biomarkers of metastatic potential.
Evidentials and metarepresentation in early child language
Authors: Ifantidou Elly
Published: April 2009

This paper examines the developmental relation of the use and understanding of Modern Greek evidential lexical items with varying degrees of metarepresentational ability. Drawing on early natural language production of two 3;6–5;10-year-olds, the paper shows that children’s use of evidentials follows a three-stage metarepresentational development. Comprehension experimental tests suggest a restricted linguistic ability and a reliable reasoning ability to interpret others’ evidential state of mind. McNemar tests which were run for the evidential linguistic pairs tested (Experiment 1) and for the evidential reasoning trials administered (Experiment 2) revealed a higher likelihood for age to affect linguistic development during 4;0–5;10 years of age, than for age to affect cognitive development of evidentiality during 3;0–5;11 years of age. The discrepancy between children’s fragile understanding of lexical evidentials and more robust recognition of consistent/conflicting evidential states is attributed to their immature metarepresentational abilities.
TEclass—a tool for automated classification of unknown eukaryotic transposable elements
Authors: Abrusán György , Grundmann Norbert , DeMester Luc , Makalowski Wojciech
Published: April 2009

Motivation: The large number of sequenced genomes required the development of software that reconstructs the consensus sequences of transposons and other repetitive elements. However, the available tools usually focus on the accurate identification of raw repeats and provide no information about the taxonomic position of the reconstructed consensi. TEclass is a tool to classify unknown transposable elements into their four main functional categories, which reflect their mode of transposition: DNA transposons, long terminal repeats (LTRs), long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs). TEclass uses machine learning support vector machine (SVM) for classification based on oligomer frequencies. It achieves 90–97% accuracy in the classification of novel DNA and LTR repeats, and 75% for LINEs and SINEs.

Availability:  http://www.compgen.uni-muenster.de/teclass, stand alone program upon request.

Contact:  abrusan@uni-muenster.de
CloudBurst: highly sensitive read mapping with MapReduce
Authors: Schatz Michael C.
Published: April 2009

Motivation: Next-generation DNA sequencing machines are generating an enormous amount of sequence data, placing unprecedented demands on traditional single-processor read-mapping algorithms. CloudBurst is a new parallel read-mapping algorithm optimized for mapping next-generation sequence data to the human genome and other reference genomes, for use in a variety of biological analyses including SNP discovery, genotyping and personal genomics. It is modeled after the short read-mapping program RMAP, and reports either all alignments or the unambiguous best alignment for each read with any number of mismatches or differences. This level of sensitivity could be prohibitively time consuming, but CloudBurst uses the open-source Hadoop implementation of MapReduce to parallelize execution using multiple compute nodes.

Results: CloudBurst's running time scales linearly with the number of reads mapped, and with near linear speedup as the number of processors increases. In a 24-processor core configuration, CloudBurst is up to 30 times faster than RMAP executing on a single core, while computing an identical set of alignments. Using a larger remote compute cloud with 96 cores, CloudBurst improved performance by >100-fold, reducing the running time from hours to mere minutes for typical jobs involving mapping of millions of short reads to the human genome.

Availability: CloudBurst is available open-source as a model for parallelizing algorithms with MapReduce at http://cloudburst-bio.sourceforge.net/.

Contact:  mschatz@umiacs.umd.edu
Oxidative stress and hyperuricaemia: pathophysiology, clinical relevance, and therapeutic implications in chronic heart failure
Authors: Bergamini Corinna , Cicoira Mariantonietta , Rossi Andrea , Vassanelli Corrado
Published: April 2009

Heart failure (HF) is a state of chronic deterioration of oxidative mechanisms due to enhanced oxidative stress and consequent subcellular alterations. In this condition, oxidant‐producing enzymes, in particular xanthine oxidase (XO), the major cardiovascular source of reactive oxygen species (ROS), are up‐regulated. Growing evidence shows that this impaired oxidative metabolism due to enhanced ROS release is implicated in the development of cardiac hypertrophy, myocardial fibrosis, left ventricular remodelling, and contractility impairment responsible for worsening of cardiac function in CHF. Uric acid (UA) has long been linked with cardiovascular diseases, and hyperuricaemia is a common finding in patients with CHF. Hyperuricaemia is associated with impairment of peripheral blood flow and reduced vasodilator capacity, which relate closely to clinical status and reduced exercise capacity. Recent studies also suggest an association between UA levels and parameters of diastolic function; more importantly, UA has emerged as a strong independent prognostic factor in patients with CHF. In this review, we describe the up‐to‐date experimental and clinical studies that have begun to test whether the inhibition of XO translates into meaningful beneficial pathophysiological changes. This treatment gives evidence that myocardial energy, endothelial dysfunction, and vasodilator reactivity to exercise are improved by reducing markers of oxidative stress responsible for vascular dysfunction, so it represents an interesting therapeutic alternative for better outcome in CHF patients.
The influence of low-frequency variability and long-term trends in North Atlantic sea surface temperature on Irish waters
Authors: Cannaby Heather , Hüsrevoğlu Y. Sinan
Published: April 2009

Cannaby, H., and Hüsrevoğlu, Y. S. 2009. The influence of low-frequency variability and long-term trends in North Atlantic sea surface temperature on Irish waters. – ICES Journal of Marine Science, 66: 1480–1489. Sea surface temperature (SST) time-series collected in Irish waters between 1850 and 2007 exhibit a warming trend averaging 0.3°C. The strongest warming has occurred since 1994, with the warmest years in the record being 2005, 2006, and 2007. The warming trend is superimposed on significant interannual to multidecadal-scale variability, linked to basin-scale oscillations of the ocean–atmosphere system. The dominant modes of low-frequency variability in North Atlantic SST records, investigated using an empirical orthogonal function (EOF) analysis, correspond to the Atlantic Multidecadal Oscillation (AMO), the East Atlantic Pattern (EAP), and the North Atlantic Oscillation (NAO) index, respectively, accounting for 23, 16, and 9% of the total variance in the dataset. Interannual variability in Irish SST records is dominated by the AMO, which, currently in its warm phase, explains approximately half of the current warm anomaly in the record. The EAP and the NAO influence variability in Irish SST time-series on a smaller scale, with the EAP also contributing to the current warm anomaly. After resolving the prevalent oscillatory modes of variability in the SST record, the underlying warming trend compares well with the global greenhouse effect warming trend. The anthropogenic contribution to the current warm anomaly in Irish SSTs was estimated at 0.41°C for 2006, and this is predicted to increase annually.
Regulating a complex adaptive system via its wasp-waist: grappling with ecosystem-based management of the New England herring fishery
Authors: Bakun Andrew , Babcock Elizabeth A. , Santora Christine
Published: April 2009

Bakun, A., Babcock, E. A., and Santora, C. 2009. Regulating a complex adaptive system via its wasp-waist: grappling with ecosystem-based management of the New England herring fishery. – ICES Journal of Marine Science, 66: 1768–1775. We use the New England herring fishery as an example of the unresolved scientific issues pertinent to ecosystem-based management of forage-fish fisheries. The biomass of herring off New England is currently well above maximum sustainable yield (BMSY), leading to pressure for expanded harvests. Associated concerns include: the maintenance of sufficiently abundant forage to meet the current needs of marine mammals and seabirds while supporting the rebuilding of overfished groundfish resources; the preservation of the service functions of a healthy population of pelagic zooplanktivorous fish to prevent possible outbreaks of pests, or hypoxia events; and the limitation of unintended bycatch of marine mammals, seabirds, and juvenile stages of groundfish. Perhaps a self-enhancing feedback loop, involving predation by herring on the early life stages of their groundfish predators, might result in regime shifts that could not be easily reversed. A plausible outcome of these ideas is a dichotomy in management choice between (i) promoting an ecosystem dominated by valuable groundfish resources and (ii) promoting the current ecosystem that features a large herring resource associated with abundant and energy-rich forage for marine mammals, seabirds, and continued high productivity of valuable shellfish resources.
Acoustic observations of micronekton fish on the scale of an ocean basin: potential and challenges
Authors: Kloser Rudy J. , Ryan Tim E. , Young Jock W. , Lewis Mark E.
Published: April 2009

Kloser, R. J., Ryan, T. E., Young, J. W., and Lewis, M. E. 2009. Acoustic observations of micronekton fish on the scale of an ocean basin: potential and challenges. – ICES Journal of Marine Science, 66: 998–1006. Acoustic methods of characterizing micronekton communities (∼2 to 20 cm length) on the scale of an ocean basin could provide valuable inputs to ecosystem-based fishery management, marine planning, and monitoring the effects of climate change. The micronekton fish are important forage for top predators (e.g. tunas), and information on their diversity, distribution, size-structure, and abundance is needed to increase accuracy of top-predator distribution and abundance predictions. At the scale of an ocean basin, four years of Tasman Sea transects using a fishing vessel provide fine-scale maps of acoustic backscatter at 38 kHz that reveal detailed spatial patterns and structure to depths of 1200 m. Research-vessel data provide detailed biodiversity, density, size structure, and acoustic-scattering information from depth-stratified net sampling and a lowered acoustic probe. Wet-weight biomass estimates of the micronekton fish in the region vary considerably by a factor of 5–58 between acoustics (16–29 g m−2), nets (1.6 g m−2), and large spatial-scale, ecological models (0.5–3 g m−2). We demonstrate the potential and challenges of an acoustic basin-scale, fishing-vessel monitoring programme, including optical and net sensing, which could assist in characterizing the biodiversity, distribution, and biomass of the micronekton fish.
Characterization of Sterol Demethylation Inhibitor-Resistant Isolates of Fusarium asiaticum and F. graminearum Collected from Wheat in China
Authors: Yin Y. , Liu X. , Li B. , Ma Z.
Published: April 2009

Fusarium asiaticum and F. graminearum are the primary causal agents of Fusarium head blight (FHB) of wheat in China. In this study, sensitivities of 159 F. asiaticum and F. graminearum isolates to a benzimidazole fungicide carbendazim (MBC) and to sterol demethylation inhibitors (DMIs) tebuconazole and prochloraz were determined. Among the 159 isolates, 9 were resistant to MBC and designated as MBC-R isolates. Three showed resistance to tebuconazole and prochloraz and designated as DMI-R isolates. There was no cross-resistance between MBC and DMI. Genetic analysis by microsatellite-primed polymerase chain reaction (PCR) showed that MBC-R or DMI-R isolates had different genotypes, which indicated that they originated from different wild-type parents. Analysis of two 14α-demethylase (cyp51) homologous genes (cyp51A and cyp51B) showed that the F. asiaticum isolates could be distinguished from F. graminearum isolates based on the sequence of cyp51A. Analysis of deduced amino acid sequence of cyp51A and cyp51B suggested that no mutations were associated with DMI resistance. Real-time PCR analysis showed that the DMI resistance was not related to the expression of cyp51A and cyp51B in F. asiaticum and F. graminearum, but expressions of both genes were induced greatly by the tebuconazole. Results of this study indicated that cyp51A would be an informative marker for analysis of population structure of F. asiaticum and F. graminearum, and the existence of homologous cyp51 genes in F. asiaticum and F. graminearum could provide new insights into DMI resistance in phytopathogenic fungi.
A Damage Function for Stem Rust of Perennial Ryegrass Seed Crops
Authors: Pfender W.
Published: April 2009

Observations of naturally occurring stem rust epidemics and seed yields in perennial ryegrass were taken in 19 field experiments conducted over the course of 9 years. Epidemic severity differed among years and also among experimental treatments (fungicide regimes) within years. In each experiment, attainable yield was represented by the nondiseased treatment, and yields of other treatments were expressed as relative yield (a proportion of the attainable yield). Yield loss (difference between attainable and actual yield) in the nonprotected treatments was 0 to 98% due to yearly differences in epidemic conditions. Fungicides were effective in reducing stem rust injury and damage when properly timed. Disease severity in the upper canopy was estimated at approximately weekly intervals and converted to proportion of the plant area diseased. The complementary value, proportion of area healthy, and its integral over time, healthy area duration (HAD), were calculated. Regression analyses were conducted using various phenological time intervals of HAD as the independent variable. The best intervals of HAD for predicting relative yield were centered on the midpoint time between anthesis and harvest. The regression equation (r2 = 0.89) for relative yield as a function of HAD during the 3-week interval was selected and rearranged to produce a quadratic damage function. This damage function estimates yield loss at 5, 22, and 42% for critical-interval diseased proportions of 1, 5, and 10%, respectively. Yield data collected from field experiments not used in model development correlated well (r2 = 0.9) with yields predicted by the damage function from their observed disease severity.
Survival, Dispersal, and Potential Soil-Mediated Suppression of Phytophthora ramorum in a California Redwood-Tanoak Forest
Authors: Fichtner E. J. , Lynch S. C. , Rizzo D. M.
Published: April 2009

Because the role of soil inoculum of Phytophthora ramorum in the sudden oak death disease cycle is not well understood, this work addresses survival, chlamydospore production, pathogen suppression, and splash dispersal of the pathogen in infested forest soils. Colonized rhododendron and bay laurel leaf disks were placed in mesh sachets before transfer to the field in January 2005 and 2006. Sachets were placed under tanoak, bay laurel, and redwood at three vertical locations: leaf litter surface, litter–soil interface, and below the soil surface. Sachets were retrieved after 4, 8, 20, and 49 weeks. Pathogen survival was higher in rhododendron leaf tissue than in bay tissue, with >80% survival observed in rhododendron tissue after 49 weeks in the field. Chlamydospore production was determined by clearing infected tissue in KOH. Moist redwood-associated soils suppressed chlamydospore production. Rain events splashed inoculum as high as 30 cm from the soil surface, inciting aerial infection of bay laurel and tanoak. Leaf litter may provide an incomplete barrier to splash dispersal. This 2-year study illustrates annual P. ramorum survival in soil and the suppressive nature of redwood-associated soils to chlamydospore production. Infested soil may serve as primary inoculum for foliar infections by splash dispersal during rain events.
Material nanosizing effect on living organisms: non-specific, biointeractive, physical size effects
Authors: Watari Fumio , Takashi Noriyuki , Yokoyama Atsuro , Uo Motohiro , Akasaka Tsukasa , Sato Yoshinori , Abe Shigeaki , Totsuka Yasunori , Tohji Kazuyuki
Published: April 2009

Nanosizing effects of materials on biological organisms was investigated by biochemical cell functional tests, cell proliferation and animal implantation testing. The increase in specific surface area causes the enhancement of ionic dissolution and serious toxicity for soluble, stimulative materials. This effect originates solely from materials and enhances the same functions as those in a macroscopic size as a catalyst. There are other effects that become prominent, especially for non-soluble, biocompatible materials such as Ti. Particle size dependence showed the critical size for the transition of behaviour is at approximately 100 μm, 10 μm and 200 nm. This effect has its origin in the biological interaction process between both particles and cells/tissue. Expression of superoxide anions, cytokines tumour necrosis factor-α and interleukin-1β from neutrophils was increased with the decrease in particle size and especially pronounced below 10 μm, inducing phagocytosis to cells and inflammation of tissue, although inductively coupled plasma chemical analysis showed no dissolution from Ti particles. Below 200 nm, stimulus decreases, then particles invade into the internal body through the respiratory or digestive systems and diffuse inside the body. Although macroscopic hydroxyapatite, which exhibits excellent osteoconductivity, is not replaced with natural bone, nanoapatite composites induce both phagocytosis of composites by osteoclasts and new bone formation by osteoblasts when implanted in bone defects. The progress of this bioreaction results in the conversion of functions to bone substitution. Although macroscopic graphite is non-cell adhesive, carbon nanotubes (CNTs) are cell adhesive. The adsorption of proteins and nano-meshwork structure contribute to the excellent cell adhesion and growth on CNTs. Non-actuation of the immune system except for a few innate immunity processes gives the non-specific nature to the particle bioreaction and restricts reaction to the size-sensitive phagocytosis. Materials larger than cell size, approximately 10 μm, behave inertly, but those smaller become biointeractive and induce the intrinsic functions of living organisms. This bioreaction process causes the conversion of functions such as from biocompatibility to stimulus in Ti-abraded particles, from non-bone substitutional to bone substitutional in nanoapatite and from non-cell adhesive to cell adhesive CNTs. The insensitive nature permits nanoparticles that are less than 200 nm to slip through body defence systems and invade directly into the internal body.
Combination of peritumoral mast cells and T‐regulatory cells predicts prognosis of hepatocellular carcinoma
Authors: Ju Min‐Jie , Qiu Shuang‐Jian , Gao Qiang , Fan Jia , Cai Ming‐Yan , Li Yi‐Wei , Tang Zhao‐You
Published: April 2009

The peritumoral inflammatory environment is critical for the progression of intrahepatic recurrence of hepatocellular carcinoma (HCC) after curative resections. Here, we investigated the relevance of peritumoral mast cells (MCs) to HCC outcomes. Peritumoral tryptase+ MCs in addition to Foxp3+ T‐regulatory cells (Tregs) were evaluated using immunohistochemistry enumeration in tissue microarrays containing 207 randomly selected HCC patients. Clinicopathological factors and postoperative outcomes were compared between high and low subgroups of MCs or Tregs. Compared to low denstiy, higher peritumoral MCs were associated with poorer clinical outcomes, and independently related to elevated 5‐year recurrence incidence (54.1%vs 39.2%, P = 0.026). High‐dense MCs were especially related to increased probability of early recurrence (within 2 years) (P = 0.004). We also found that peritumoral Tregs were positively correlated with MCs in density (r = 0.353, P < 0.001) and reversely related to HCC outcomes. Notably, MCs in combination with Tregs displayed better prognostic performances than MCs alone (area under curve [AUC]survival = 0.629 vs 0.589, AUCrecurrence = 0.632 vs 0.591). Moreover, MCs were positively correlated to alanine aminotransferase, a serum inflammatory marker (P = 0.014). Therefore, peritumoral MCs are promising prognostic parameters for HCC mainly through inflammation response–related mechanisms, and we propose that MCs and Tregs may cooperate with each other and result in poorer prognosis. (Cancer Sci 2009; 100: 1267–1274)
Do the Transtheoretical Model processes of change, decisional balance and temptation predict stage movement? Evidence from smoking cessation in adolescents
Authors: Guo Boliang , Aveyard Paul , Fielding Antony , Sutton Stephen
Published: April 2009

Aims  To examine the effects of processes of change (POC) on forward stage movement directly, indirectly through decisional balance and temptation, and total effects as a test of the key hypothesis of the Transtheoretical Model (TTM).

Design  Prospective cohort study.

Setting  United Kingdom.

Participants  A total of 1160 adolescents aged 13–14 years who were current or former smokers at baseline.

Measurements  Stage was assessed with the standard algorithm three times, once every 3 months. On each occasion the POC, decisional balance and temptation were measured with the standard questionnaires. Path analysis was used to examine the direct, indirectly mediated and total contribution of POC and the other constructs to stage movement 3 months later.

Findings  Four of the 24 analyses showed evidence that the theoretically appropriate POC predicted stage transition, with statistically significant total effects. Effect sizes were small. When the POC were summarized to experiential and behavioural process means, one transition from pre‐contemplation was predicted by experiential processes and, contrary to the TTM, one transition predicted by behavioural processes. There was slightly more evidence that decisional balance (attitudes towards smoking) and temptation (ability to resist the urge to smoke) was associated with stage transition.

Conclusions  POC use was not associated generally with stage transition and evidence that effects, if missed, must be modest, giving no support to the central tenet of the TTM.
Substance use and misuse in the aftermath of terrorism. A Bayesian meta‐analysis
Authors: DiMaggio Charles , Galea Sandro , Li Guohua
Published: April 2009

Aim  To conduct a comprehensive analysis of the conflicting evidence on substance use and misuse following mass traumas such as terrorist incidents.

Methods  We reviewed and synthesized evidence from 31 population‐based studies using Bayesian meta‐analysis and meta‐regression.

Results  The majority of the studied were conducted in the aftermath of the terrorist attacks of 11 September 2001. Controlling for exposure, type of incident and time since the event occurred, 7.3% [95% credible interval (CrI) 1.1–32.5%] of a population can be expected to report increased alcohol consumption in the first 2 years following a terrorist event. There is, however, a 20% probability that the prevalence will be as high as 14%. The unadjusted prevalence of increased cigarette smoking following a terrorist event is 6.8% (95% Cr I 2.6–16.5%). Unadjusted reports of mixed drug use (including narcotics and prescription medications) was 16.3% (95% Cr I 1.3–72.5%).

Conclusions  These results underscore the potentially pervasive behavioral health effects of mass terrorism, and suggest that public health interventions may usefully consider substance use as an area of focus after such events.
Prevalence and clinical relevance of corrected QT interval prolongation during methadone and buprenorphine treatment: a mortality assessment study
Authors: Anchersen Katinka , Clausen Thomas , Gossop Michael , Hansteen Viggo , Waal Helge
Published: April 2009

Aims  To determine the prevalence of corrected QT interval (QTc) prolongation among patients in opioid maintenance treatment (OMT) and to investigate mortality potentially attributable to QTc prolongation in the Norwegian OMT programme.

Participants and setting  Two hundred OMT patients in Oslo were recruited to the QTc assessment study between October 2006 and August 2007. The Norwegian register of all patients receiving OMT in Norway (January 1997–December 2003) and the national death certificate register were used to assess mortality. Mortality records were examined for the 90 deaths that had occurred among 2382 patients with 6450 total years in OMT.

Design and measures  The QTc interval was assessed by electrocardiography (ECG). All ECGs were examined by the same cardiologist, who was blind to patient history and medication. Mortality was calculated by cross‐matching the OMT register and the national death certificate register: deaths that were possibly attributable to QTc prolongation were divided by the number of patient‐years in OMT.

Findings  In the QTc assessment sample (n = 200), 173 patients (86.5%) received methadone and 27 (13.5%) received buprenorphine. In the methadone group, 4.6% (n = 8) had a QTc above 500 milliseconds; 15% (n = 26) had a QTc interval above 470 milliseconds; and 28.9% (n = 50) had a QTc above 450 milliseconds. All patients receiving buprenorphine (n = 27) had QTc results <450 milliseconds. A positive dose‐dependent association was identified between QTc length and dose of methadone, and all patients with a QTc above 500 milliseconds were taking methadone doses of 120 mg or more. OMT patient mortality, where QTc prolongation could not be excluded as the cause of death, was 0.06/100 patient‐years. Only one death among 3850 OMT initiations occurred within the first month of treatment.

Conclusion  Of the methadone patients, 4.6% had QTc intervals above 500 milliseconds. The maximum mortality attributable to QTc prolongation was low: 0.06 per 100 patient‐years.
Keratin 18 provides resistance to Fas‐mediated liver failure in mice
Authors: Leifeld L. , Kothe S. , Söhl G. , Hesse M. , Sauerbruch T. , Magin T. M. , Spengler U.
Published: April 2009

Background  Keratins are intermediate filament proteins of epithelial cells with pivotal functions for cell integrity. They comprise keratins 18 [K18] and 8 [K8] in hepatocytes. Keratins are of major importance for an intact cellular microarchitecture and have protective functions in human liver diseases. In mice, K8 has been demonstrated to protect against Fas‐antibody‐induced liver failure by direct interaction with apoptotic regulators, while the role of K18 remains unresolved.

Materials and methods  We analysed effects of K18 deficiency on Fas‐induced liver failure in mice. We determined survival and analysed induction of apoptosis after injection of the agonistic Fas antibody Jo2 into K18−/− and wild‐type control mice by TUNEL assay and fluorometrically analysed caspase‐3, ‐8 and ‐9 activities 1, 2 and 3 h after Jo2 injection.

Results  In K18−/− mice, survival of Fas‐antibody treated mice was significantly shorter than that of wild‐type controls (P = 0·02). However, shortened survival of K18−/− mice was caused by increased hepatic damage but was not correlated to enhanced induction of apoptotic pathways, as neither numbers of TUNEL positive apoptotic cells nor activities of caspases‐3, ‐8 and ‐9 differed between K18−/− and K18+/+ mice at any point of time.

Conclusion  K18−/− mice are significantly more susceptible to Fas‐antibody‐induced liver failure. The cytoprotective effect of K18 is not explained by a differential activation of caspases‐3, ‐8 and ‐9, suggesting that K18 does not directly interfere with apoptotic regulators. Importantly, however, K18 exerts significant protective functions by other mechanisms.
Complications of hysterectomy in women with von Willebrand disease
Authors: JAMES A. H. , MYERS E. R. , COOK C. , PIETROBON R.
Published: April 2009

Summary.  Case reports and small case series suggest that women with von Willebrand disease (VWD) are at a very high risk of bleeding complications with hysterectomy. As the procedure may be beneficial to women who suffer from heavy menstrual bleeding and have completed childbearing, an understanding of the true risks involved is essential for appropriate decision making. To estimate the incidence of bleeding and other complications in women with VWD who undergo hysterectomy. The United States Nationwide Inpatient Sample (NIS) from the Healthcare Cost and Utilization Project of the Agency for Healthcare Research and Quality for the years 1988–2004 was queried for all hysterectomies for non‐malignant conditions. Data were analysed based on the NIS sampling design. Bivariate analyses were used to examine the differences between women with and without VWD. Multivariate analysis was used to adjust for potential confounders among women who underwent hysterectomy for heavy menstrual bleeding. 545 of the 1 358 133 hysterectomies were to women with VWD. Women with VWD were significantly more likely to experience intraoperative and postoperative bleeding (2.75% vs. 0.89%, P < 0.001) and require transfusion (7.34% vs. 2.13%, P < 0.001) than women without VWD. One woman with VWD died. While the risk of bleeding complications from hysterectomy in women with VWD is smaller than previously reported, women with VWD did experience significantly more bleeding complications than women without VWD. Nonetheless, for women who have completed childbearing, the risks of hysterectomy may be acceptable.
Functional roles of the factor VIII B domain
Authors: PIPE S. W.
Published: April 2009

Summary.  Unravelling the structure, function and molecular interactions of factor VIII (FVIII) throughout its life cycle from biosynthesis to clearance has advanced our understanding of the molecular mechanisms of haemophilia and the development of effective treatment strategies including recombinant replacement therapy. These insights are now influencing bioengineering strategies toward novel therapeutics. Whereas available molecular models and crystal structures have helped elucidate the structure and function of the A and C domains of FVIII, these models have not included detailed structural information of the B domain. Therefore, insights into the role of the FVIII B domain have come primarily from expression studies in heterologous systems, biochemical studies on bioengineered FVIII variants and clinical studies with B domain‐deleted FVIII. This manuscript reviews the available data on the potential functional roles of the FVIII B domain. A detailed literature search was performed, and the data extracted were qualitatively summarized. Intriguing emerging evidence suggests that the FVIII B domain is involved in intracellular interactions that regulate quality control and secretion, as well as potential regulatory roles within plasma during activation, platelet binding, inactivation and clearance.
Clinical evaluation of moroctocog alfa (AF‐CC), a new generation of B‐domain deleted recombinant factor VIII (BDDrFVIII) for treatment of haemophilia A: demonstration of safety, efficacy, and pharmacokinetic equivalence to full‐length recombinant factor VIII
Authors: RECHT M. , NEMES L. , MATYSIAK M. , MANCO‐JOHNSON M. , LUSHER J. , SMITH M. , MANNUCCI P. , HAY C. , ABSHIRE T. , O’BRIEN A. , HAYWARD B. , UDATA C. , ROTH D.A. , ARKIN S.
Published: April 2009

Summary.  BDDrFVIII is a B‐domain deleted recombinant factor VIII (rFVIII) product for haemophilia A. Manufacture uniquely includes purification chromatography by synthetic‐affinity ligand rather than murine‐based monoclonal antibody, as well as an albumin‐free cell culture process. BDDrFVIII was studied in 204 patients, including 62 subjects <16 years old, in two studies. A double‐blind, randomized, pharmacokinetic (PK) crossover study, utilizing a central laboratory assay (one‐stage (OS)) for both drug potency assignment and plasma FVIII‐activity measurements, demonstrated that BDDrFVIII was PK‐equivalent to a full‐length rFVIII. Favourable efficacy and safety were observed: during defined routine prophylaxis in a patient population significant for preexisting target joints, nearly half (45.7%) of patients had no bleeding, and a low‐annualized bleed rate (ABR) was achieved (median 1.9); 92.5% of haemorrhages (n = 187) required ≤2 infusions. Three subjects (1.5%, across both studies) developed de novo inhibitors (low‐titre, transient), and the primary safety endpoint, based on a prospective Bayesian analysis, demonstrated the absence of neoantigenicity for BDDrFVIII. The PK‐equivalence, based on central testing to align test and reference articles, and the novel Bayesian analysis of inhibitor safety in these investigations reflect robust experimental designs with relevance to future studies. This extensive dataset demonstrates the safety and efficacy of BDDrFVIII for haemophilia A.
Health‐related quality of life and productivity impact in haemophilia patients with inhibitors
Authors: BROWN T. M. , LEE W. C. , JOSHI A. V. , PASHOS C. L.
Published: April 2009

Summary.  To measure health‐related quality of life (HRQL), its determinants, and its association with patient and caregiver productivity among a sample of haemophilia patients with inhibitors in the United States (US). Data on demographical and clinical characteristics, treatment patterns, HRQL (SF‐12v2), and productivity outcomes were reported for 53 patients. Mean SF‐12v2 domain and mental (MCS) and physical (PCS) component summary scores were assessed and compared with US norms. Regression analyses explored the association of patient and treatment factors with HRQL and productivity. Patients’ mean age was 20.7 years (SD = 18.8), 88.5% were type A, and 39.6% received on‐demand therapy as their only mode of treatment. Mean PCS was significantly lower than the US norm (PCS, 39.9, P < 0.01) and mean MCS showed no significant difference (MCS, 49.9, P = ns). On‐demand treatment (B = −0.336, P < 0.05) and number of haemorrhages (B = −0.366, P < 0.05) were negatively associated with PCS; and PCS was associated with patients’ missed work or school days [incidence rate ratio (IRR) = 0.93, P < 0.001] and perceived impact on daily activities (OR = 0.72, P < 0.05). Younger age (IRR = 0.91, P < 0.01), lower PCS (IRR = 0.94, P < 0.01), more haemorrhages (IRR = 1.05, P < 0.05), and surgery (IRR = 2.74, P < 0.05) were associated with fewer patients’ productive days. Physical functioning among inhibitor patients in the US is compromised and is negatively associated with their daily activities and productivity. These data suggest a positive association of prophylactic and immunotolerance therapy with HRQL, specifically physical impairment.
Manipulation of plant innate immunity and gibberellin as factor of compatibility in the mutualistic association of barley roots with Piriformospora indica
Authors: Schäfer Patrick , Pfiffi Stefanie , Voll Lars M. , Zajic Doreen , Chandler Peter M. , Waller Frank , Scholz Uwe , Pons‐Kühnemann Jörn , Sonnewald Sophia , Sonnewald Uwe , Kogel Karl‐Heinz
Published: April 2009

Fungi of the order Sebacinales (Basidiomycota) are involved in a wide spectrum of mutualistic symbioses with various plants, thereby exhibiting unique potential for biocontrol strategies. Piriformospora indica, a model organism of this fungal order, is able to increase the biomass and grain yield of crop plants, and induces local and systemic resistance to fungal diseases and tolerance to abiotic stress. To elucidate the molecular basis for root colonization, we characterized the interaction of P. indica with barley roots by combining global gene expression profiling, metabolic profiling, and genetic studies. At the metabolic level, we show that fungal colonization reduces the availability of free sugars and amino acids to the root tip. At the transcriptional level, consecutive interaction stages covering pre‐penetration‐associated events and progressing through to root colonization showed differential regulation of signal perception and transduction components, secondary metabolism, and genes associated with membrane transport. Moreover, we observed stage‐specific up‐regulation of genes involved in phytohormone metabolism, mainly encompassing gibberellin, auxin and abscisic acid, but salicylic acid‐associated gene expression was suppressed. The changes in hormone homoeostasis were accompanied with a general suppression of the plant innate immune system. Further genetic studies showed reduced fungal colonization in mutants that are impaired in gibberellin synthesis as well as perception, and implicate gibberellin as a modulator of the root’s basal defence. Our data further reveal the complexity of compatibility mechanisms in host–microbe interactions, and identify gibberellin signaling as potential target for successful fungi.
The insecticidal activity of four medicinal plants against the blowfly Lucilia sericata (Diptera: Calliphoridae)
Authors: Khater Hanem Fathy , Khater D. F.
Published: April 2009

Background  The larvae of Lucilia sericata induce myiasis and transmit mycobacterial infections to humans and animals. Consequently, the blowfly should be controlled for human welfare and economic reasons.

Methods  The insecticidal effect of fenugreek (Trigonella foenum‐graecum), celery (Apium graveolens), radish (Raphanus sativus), and mustard (Brassica compestris) against the third larval instars of L. sericata was evaluated, for the first time, through ingestion assays. The effect of sublethal concentrations on certain biological aspects, such as the pupation rates and adult emergence, was revealed.

Results  The LC50 values were 2.81, 4.60, 6.93, and 7.92% for fenugreek, celery, radish, and mustard, respectively. The adverse effects on larval treatment also included the survival of pupae and adults. The pupation rate was strongly decreased after treatment with 16% fenugreek and celery. Moreover, adult emergence was suppressed after treatment of larvae with 8% mustard, 12% radish, and 16% fenugreek and celery oils. The number of emerged males exceeded the number of females, which could lead to population decline. Morphologic abnormalities of larvae, pupae, and adults were recorded after treatment with all tested oils.

Conclusion  The results suggest that oils may represent new and safe potential insecticides for the control of blowflies.
HLA‐A*1136 and HLA‐A*1138 were identified by polymerase chain reaction sequence‐based typing in Chinese individuals
Authors: Zhu F.‐M. , Zhang W. , Xu X. G. , Yan L.‐X.
Published: April 2009

Two human leukocyte antigen (HLA)‐A*11 variant alleles were identified in Chinese individuals. HLA‐A*1136 shows only one nucleotide difference from A*110101 in exon 3 at position 368, resulting in an amino acid change from His to Cys at codon 99. HLA‐A*1138 has two nucleotides change at positions 570 and 571 compared with A*110201, resulting in amino acids change from Glu to Asp at codon 166 and Trp to Gly at codon 167.
Treatment of Strongyloides stercoralis hyperinfection‐associated septic shock and acute respiratory distress syndrome with drotrecogin alfa (activated) in a renal transplant recipient
Authors: Huston J.M. , Eachempati S.R. , Rodney J.R. , Cayci C. , Fusco D. , Mathew M. , Shou J. , Goldstein M.J. , Kapur S. , Barie P.S.
Published: April 2009

Abstract: We report a case of Strongyloides stercoralis hyperinfection syndrome in a renal transplant recipient complicated by septic shock, acute respiratory distress syndrome, and Klebsiella pneumoniae superinfection. The patient was treated successfully with drotrecogin alfa (activated), parenteral ivermectin, albendazole, and piperacillin/tazobactam. This outcome suggests that drotrecogin alfa (activated) may be useful therapy for transplant recipients who develop severe sepsis or septic shock secondary to potentially lethal opportunistic infections.
Provenance and thermal history of the Bayan Har Group in the western‐central Songpan–Ganzi–Bayan Har terrane: Implications for tectonic evolution of the northern Tibetan Plateau
Authors: Wang Guo‐Can , Wintsch Robert P. , Garver John I. , Roden‐Tice Mary , Chen She‐Fa , Zhang Ke‐Xin , Lin Qi‐Xiang , Zhu Yun‐Hai , Xiang Shu‐Yuan , Li De‐Wei
Published: April 2009

Triassic turbidites dominate the Songpan–Ganzi–Bayan Har (SGBH) terrane of the northern Tibetan Plateau. U‐Pb dating on single detrital zircon grains from the Triassic Bayan Har Group turbidites yield peaks at 400–500 m.y., 900–1000 m.y., 1800–1900 m.y., and 2400–2500 m.y., These results are consistent with recently published U‐Pb zircon ages of pre‐Triassic bedrock in the East Kunlun, Altyn, Qaidam, Qilian and Alaxa areas to the north, suggesting that provenance of the Bayan Har Group may include these rocks. The similarities in the compositions of the lithic arkosic sandstones of the Bayan Har Group with the sandstones of the Lower‐Middle Triassic formations in the East Kunlun terrane to the north also suggests a common northern provenance for both. A well exposed angular unconformity between the Carboniferous–Middle Permian mélange sequences and the overlying Upper Permian or Triassic strata indicates that regional deformation occurred between the Middle and Late Permian. This deformation may have been the result of a soft collision between the Qiangtang terrane and the North China Plate and the closure of the Paleo‐Tethyan oceanic basin. The Bayan Har Group turbidites were then deposited in a re‐opened marine basin on a shelf environment. Fission‐track dating of detrital zircons from the Bayan Har Group sandstones revealed pre‐ and post‐depositional age components, suggesting that the temperatures did not reach the temperatures necessary to anneal retentive zircon fission tracks (250–300°C). A 282–292 m.y. peak age defined by low U concentration, retentive zircons likely reflects a northern granitic source. Euhedral zircons from two lithic arkoses with abundant volcanic fragments in the southern area yielded a ∼237 m.y. zircon fission track (ZFT) peak age, likely recording the maximum age of deposition. A dominant post‐depositional 170–185 m.y. ZFT peak age suggests peak temperatures were reached in the Early Jurassic. Some samples appear to record a younger thermal event at ∼140 m.y., a short lived event that apparently affected only the least retentive zircons.
Therapeutic embolization of systemic arterial supply to normal basal segments of the left lower lobe of the lung
Authors: LIM Hee Hwan , HUH Jeong Kwon , KIM Jung Hoon , NO Hee Sun , CHOE Du Hwan , KIM Cheol Hyeon , LEE Jae Cheol
Published: April 2009

Systemic arterialization of normal lung without sequestration is a rare congenital abnormality. The basal segments of the left lower lobe are most frequently involved. The involved lung has no structural abnormalities of the tracheobronchial tree that distinguish this abnormality from bronchopulmonary sequestration. Haemoptysis and exertional dyspnoea are common presenting symptoms. We report the case of a 26‐year‐old man who presented with recurrent haemoptysis due to systemic arterialization of basal segments of the left lower lobe of the lung, without sequestration. Therapeutic embolization using metallic coils was successfully performed without any complications. There was no further haemoptysis during a 6‐month follow up. Therapeutic embolization is a safe and effective method of managing the haemoptysis associated with aberrant systemic arterial supply to the normal lung.