bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidemiologic Investigation of a 2007 Outbreak of Serratia marcescens Bloodstream Infection in Texas Caused by Contamination of Syringes Prefilled With Heparin and Saline
Authors: Su John R. , Blossom David B. , Chung Wendy , Gullion Jessica Smartt , Pascoe Neil , Heseltine Gary , Srinivasan Arjun
Published: May 2009

This retrospective cohort study found that syringes prefilled with heparin flush solution caused an outbreak of Serratia marcescens bloodstream infection at an outpatient treatment center in Texas in 2007. The epidemiologic study supported this conclusion, despite the lack of microbiologic evidence of contamination from environmental and product testing. This report underscores the crucial contributions that epidemiologic studies can make to investigations of outbreaks that are possibly product related.
MetNetAligner: a web service tool for metabolic network alignments
Authors: Cheng Qiong , Harrison Robert , Zelikovsky Alexander
Published: May 2009

Summary: The accumulation of high-throughput genomic, proteomic and metabolical data allows for increasingly accurate modeling and reconstruction of metabolic networks. Alignment of the reconstructed networks can help to catch model inconsistencies and infer missing elements. In this note, we present the web service tool MetNetAligner which aligns metabolic networks, taking in account the similarity of network topology and the enzymes' functions. It can be used for predicting unknown pathways, comparing and finding conserved patterns and resolving ambiguous identification of enzymes. The tool supports several alignment options including allowing or forbidding enzyme deletion and insertion. It is based on a novel scoring scheme which measures enzyme-to-enzyme functional similarity and a fast algorithm which efficiently finds optimal mappings from a directed graph with restricted cyclic structure to an arbitrary directed graph.

Availability: MetNetAligner is available as web-server at: http://alla.cs.gsu.edu:8080/MinePW/pages/gmapping/GMMain.html.

Contact:  alexz@cs.gsu.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
A tool for identification of genes expressed in patterns of interest using the Allen Brain Atlas
Authors: Davis Fred P. , Eddy Sean R.
Published: May 2009

Motivation: Gene expression patterns can be useful in understanding the structural organization of the brain and the regulatory logic that governs its myriad cell types. A particularly rich source of spatial expression data is the Allen Brain Atlas (ABA), a comprehensive genome-wide in situ hybridization study of the adult mouse brain. Here, we present an open-source program, ALLENMINER, that searches the ABA for genes that are expressed, enriched, patterned or graded in a user-specified region of interest.

Results: Regionally enriched genes identified by ALLENMINER accurately reflect the in situ data (95–99% concordance with manual curation) and compare with regional microarray studies as expected from previous comparisons (61–80% concordance). We demonstrate the utility of ALLENMINER by identifying genes that exhibit patterned expression in the caudoputamen and neocortex. We discuss general characteristics of gene expression in the mouse brain and the potential application of ALLENMINER to design strategies for specific genetic access to brain regions and cell types.

Availability: ALLENMINER is freely available on the Internet at http://research.janelia.org/davis/allenminer.

Contact:  davisf@janelia.hhmi.org

Supplementary information:  Supplementary data are available at Bioinformatics online.
U-Compare: share and compare text mining tools with UIMA
Authors: Kano Yoshinobu , Baumgartner William A. , McCrohon Luke , Ananiadou Sophia , Cohen K. Bretonnel , Hunter Lawrence , Tsujii Jun'ichi
Published: May 2009

Summary: Due to the increasing number of text mining resources (tools and corpora) available to biologists, interoperability issues between these resources are becoming significant obstacles to using them effectively. UIMA, the Unstructured Information Management Architecture, is an open framework designed to aid in the construction of more interoperable tools. U-Compare is built on top of the UIMA framework, and provides both a concrete framework for out-of-the-box text mining and a sophisticated evaluation platform allowing users to run specific tools on any target text, generating both detailed statistics and instance-based visualizations of outputs. U-Compare is a joint project, providing the world's largest, and still growing, collection of UIMA-compatible resources. These resources, originally developed by different groups for a variety of domains, include many famous tools and corpora. U-Compare can be launched straight from the web, without needing to be manually installed. All U-Compare components are provided ready-to-use and can be combined easily via a drag-and-drop interface without any programming. External UIMA components can also simply be mixed with U-Compare components, without distinguishing between locally and remotely deployed resources.

Availability:  http://u-compare.org/

Contact:  kano@is.s.u-tokyo.ac.jp
apLCMS—adaptive processing of high-resolution LC/MS data
Authors: Yu Tianwei , Park Youngja , Johnson Jennifer M. , Jones Dean P.
Published: May 2009

Motivation: Liquid chromatography-mass spectrometry (LC/MS) profiling is a promising approach for the quantification of metabolites from complex biological samples. Significant challenges exist in the analysis of LC/MS data, including noise reduction, feature identification/ quantification, feature alignment and computation efficiency.

Result: Here we present a set of algorithms for the processing of high-resolution LC/MS data. The major technical improvements include the adaptive tolerance level searching rather than hard cutoff or binning, the use of non-parametric methods to fine-tune intensity grouping, the use of run filter to better preserve weak signals and the model-based estimation of peak intensities for absolute quantification. The algorithms are implemented in an R package apLCMS, which can efficiently process large LC/ MS datasets.

Availability: The R package apLCMS is available at www.sph.emory.edu/apLCMS.

Contact:  tyu8@sph.emory.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
PESTAS: a web server for EST analysis and sequence mining
Authors: Nam Seong-Hyeuk , Kim Dae-Won , Jung Tae-Sung , Choi Young-Sang , Kim Dong-Wook , Choi Han-Suk , Choi Sang-Haeng , Park Hong-Seog
Published: May 2009

Summary: We have developed a web server for the high-throughput annotation of expressed sequence tags (ESTs) called pipeline for EST analysis service (PESTAS). PESTAS processes entire datasets with an automated pipeline of 13 analytic services, then deposits the data into the MySQL database and transforms it into three kinds of reports: preprocessing, assembling and annotation. All annotated information is provided to the scientist and can be downloaded through a web browser. To get more relevant functional annotation results, a curation function was introduced with which biologists can easily change the best-hit annotation information. We included a gene chip module that detects gene expression differences between libraries by comparing accession number counts from BLAST search results. PESTAS also provides access to the pathway information of KEGG, which is useful for mapping the relationships among networks of annotated enzymes, and is especially valuable for those researchers interested in biological pathways.

Availability: PESTAS is available at http://pestas.kribb.re.kr/

Supplementary information: Supplementary data are available at http://pestas.kribb.re.kr/pestas.jsp.

Contact:  odysseus@kribb.re.kr
Structural insights into eRF3 and stop codon recognition by eRF1
Authors: Cheng Zhihong , Saito Kazuki , Pisarev Andrey V. , Wada Miki , Pisareva Vera P. , Pestova Tatyana V. , Gajda Michal , Round Adam , Kong Chunguang , Lim Mengkiat , Nakamura Yoshikazu , Svergun Dmitri I. , Ito Koichi , Song Haiwei
Published: May 2009

Eukaryotic translation termination is mediated by two interacting release factors, eRF1 and eRF3, which act cooperatively to ensure efficient stop codon recognition and fast polypeptide release. The crystal structures of human and Schizosaccharomyces pombe full-length eRF1 in complex with eRF3 lacking the GTPase domain revealed details of the interaction between these two factors and marked conformational changes in eRF1 that occur upon binding to eRF3, leading eRF1 to resemble a tRNA molecule. Small-angle X-ray scattering analysis of the eRF1/eRF3/GTP complex suggested that eRF1's M domain contacts eRF3's GTPase domain. Consistently, mutation of Arg192, which is predicted to come in close contact with the switch regions of eRF3, revealed its important role for eRF1's stimulatory effect on eRF3's GTPase activity. An ATP molecule used as a crystallization additive was bound in eRF1's putative decoding area. Mutational analysis of the ATP-binding site shed light on the mechanism of stop codon recognition by eRF1.
Genome-wide replication profiles indicate an expansive role for Rpd3L in regulating replication initiation timing or efficiency, and reveal genomic loci of Rpd3 function inSaccharomyces cerevisiae
Authors: Knott Simon R.V. , Viggiani Christopher J. , Tavaré Simon , Aparicio Oscar M.
Published: May 2009

In higher eukaryotes, heritable gene silencing is associated with histone deacetylation and late replication timing. InSaccharomyces cerevisiae, the histone deacetylase Rpd3 regulates gene expression and also modulates replication timing; however, these mechanisms have been suggested to be independent, and no global association has been found between replication timing and gene expression levels. Using 5-Bromo-2′-deoxyuridine (BrdU) incorporation to generate genome-wide replication profiles, we identified >100 late-firing replication origins that are regulated by Rpd3L, which is specifically targeted to promoters to silence transcription. Rpd3S, which recompacts chromatin after transcription, plays a primary role at only a handful of origins, but subtly influences initiation timing globally. The ability of these functionally distinct Rpd3 complexes to affect replication initiation timing supports the idea that histone deacetylation directly influences initiation timing. Accordingly, loss of Rpd3 function results in higher levels of histone H3 and H4 acetylation surrounding Rpd3-regulated origins, and these origins show a significant association with Rpd3 chromatin binding and gene regulation, supporting a general link between histone acetylation, replication timing, and control of gene expression in budding yeast. Our results also reveal a novel and complementary genomic map of Rpd3L- and Rpd3S-regulated chromosomal loci.
Life on the edge: telomeres and persistent DNA breaks converge at the nuclear periphery: Figure 1.
Authors: Gartenberg Marc R.
Published: May 2009

Persistent DNA double-strand breaks and telomeres represent genomic hazards, as they can instigate inappropriate repair reactions. Two recent papers by Oza and colleagues (pp. 912–917) and Schober and colleagues (pp. 928–938) show that both types of DNA ends are sequestered from bulk DNA by Mps3, a SUN domain protein that spans the inner nuclear membrane. Anchorage maintains telomere integrity and steers double-strand breaks toward specialized repair pathways. This work defines the nuclear periphery as a subcompartment where dangerous DNA elements can be handled with care.
Chromatin-based transcriptional punctuation: Figure 1.
Authors: Talbert Paul B. , Henikoff Steven
Published: May 2009

The long polycistronic transcription units of trypanosomes do not appear to be demarcated by the usual DNA motifs that punctuate transcription in familiar eukaryotes. In this issue of Genes & Development, Siegel and colleagues (pp. 1063–1076) describe a system for the demarcation of trypanosome transcription units based on the deposition and turnover of histone variants rather than on the binding of transcription factors. Replication-independent incorporation of histone variants and destabilization of nucleosomes is an emerging theme at promoters of more familiar eukaryotes, and it now appears that this system is an evolutionarily conserved mode of transcriptional punctuation.
Yeast mitochondrial Gln-tRNAGln is generated by a GatFAB-mediated transamidation pathway involving Arc1p-controlled subcellular sorting of cytosolic GluRS
Authors: Frechin Mathieu , Senger Bruno , Brayé Mélanie , Kern Daniel , Martin Robert Pierre , Becker Hubert Dominique
Published: May 2009

It is impossible to predict which pathway, direct glutaminylation of tRNAGln or tRNA-dependent transamidation of glutamyl-tRNAGln, generates mitochondrial glutaminyl-tRNAGln for protein synthesis in a given species. The report that yeast mitochondria import both cytosolic glutaminyl-tRNA synthetase and tRNAGln has challenged the widespread use of the transamidation pathway in organelles. Here we demonstrate that yeast mitochondrial glutaminyl-tRNAGln is in fact generated by a transamidation pathway involving a novel type of trimeric tRNA-dependent amidotransferase (AdT). More surprising is the fact that cytosolic glutamyl-tRNA synthetase (cERS) is imported into mitochondria, where it constitutes the mitochondrial nondiscriminating ERS that generates the mitochondrial mischarged glutamyl-tRNAGln substrate for the AdT. We show that dual localization of cERS is controlled by binding to Arc1p, a tRNA nuclear export cofactor that behaves as a cytosolic anchoring platform for cERS. Expression of Arc1p is down-regulated when yeast cells are switched from fermentation to respiratory metabolism, thus allowing increased import of cERS to satisfy a higher demand of mitochondrial glutaminyl-tRNAGln for mitochondrial protein synthesis. This novel strategy that enables a single protein to be localized in both the cytosol and mitochondria provides a new paradigm for regulation of the dynamic subcellular distribution of proteins between membrane-separated compartments.
The Meaning of Autonomy: On and Beyond the Interpersonal Circumplex
Authors: Hmel Beverly A . , Pincus Aaron L .
Published: May 2009

ABSTRACT Review of existing psychological literature suggests that conceptions of autonomy as an individual difference have taken several forms. Structural analyses of 15 self‐report autonomy scales utilizing the interpersonal circumplex (IPC) and the Five‐Factor Model (FFM) of personality as structural referents confirmed the presence of diverse conceptualizations of this construct. Two hundred ninety undergraduate students completed 15 autonomy scales, the NEO Personality Inventory–Revised (NEO‐PI‐R), and the Interpersonal Adjective Scales (IAS). Factor analysis revealed three unique conceptualizations of autonomy. Each factor was further differentiated from the others by its unique location on the IPC and its distinct relationships with the domains and facets of the NEO‐PI‐R. Evaluation of these findings within the context of existing autonomy research leads to the conclusion that only two of the three identified factors reflect autonomy. Factor I, Depressogenic Vulnerability, though relatively consistent with its theoretical foundation, lacks the agentic quality one would expect in an autonomy construct. Factors II and III, presently labeled Self‐governance and Agentic Separation, respectively, share an agentic core but differ considerably in their interpersonal content. Theoretical and empirical implications of these findings are discussed.
Life‐Satisfaction Is a Momentary Judgment and a Stable Personality Characteristic: The Use of Chronically Accessible and Stable Sources
Authors: Schimmack Ulrich , Diener Ed , Oishi Shigehiro
Published: May 2009

ABSTRACT Social cognition research indicates that life‐satisfaction judgments are based on a selected set of relevant information that is accessible at the time of the life‐satisfaction judgment. Personality research indicates that life‐satisfaction judgments are quite stable over extended periods of time and predicted by personality traits. The present article integrates these two research traditions. We propose that people rely on the same sources to form repeated life‐satisfaction judgments over time. Some of these sources (e.g., memories of emotional experiences, academic performance) provide stable information that explains the stability in life‐satisfaction judgments. Second, we propose that the influence of personality traits on life satisfaction is mediated by the use of chronically accessible sources because traits produce stability of these sources. Most important, the influence of extraversion and neuroticism is mediated by use of memories of past emotional experiences. To test this model, participants repeatedly judged life‐satisfaction over the course of a semester. After each assessment, participants reported sources that they used for these judgments. Changes in reported sources were related to changes in life‐satisfaction judgments. A path model demonstrated that chronically accessible and stable sources are related to stable individual differences in life‐satisfaction. Furthermore, the model supported the hypothesis that personality effects were mediated by chronically accessible and stable sources. In sum, the results are consistent with our theory that life‐satisfaction judgments are based on chronically accessible sources.
Cost‐effectiveness of biological therapy for Crohn’s disease: Markov cohort analyses incorporating United Kingdom patient‐level cost data
Authors: BODGER K. , KIKUCHI T. , HUGHES D.
Published: May 2009

Background  Anti‐TNF‐alpha agents for Crohn's disease (CD) have good clinical efficacy but high acquisition cost compared to rival drugs.

Aim  To assess the cost‐effectiveness of infliximab and adalimumab for Crohn’s disease from the perspective of the UK NHS, incorporating recent trial and observational data.

Methods  Lifetime Markov analyses constructed to simulate quality‐adjusted life‐years (QALYs) and costs. CD was represented by four health‐states representing: Full response, partial response, nonresponse, surgery and death. The course of CD under standard care was based on the Olmsted county cohort. Systematic review identified ACCENT I (infliximab) and CHARM (adalimumab) as sources for efficacy data. We modelled an intention‐to‐treat strategy for biologics including surgical rates based on observational data, cost estimates from our UK dataset and utilities from an algorithm converting CDAI to EQ‐5D utilities.

Results  The incremental cost‐effectiveness ratios (ICERs) compared to standard care for 1‐year of treatment with infliximab or adalimumab were £19 050 and £7190 per QALY gained, respectively. Lifetime therapy was dominated by standard care. Analyses over shorter time horizons, matched to treatment duration, resulted in unfavourable ICERs.

Conclusion  The model suggests acceptable ICERs for biological agents when considering a lifetime horizon with periods of up to 4 years continuous therapy. As with all economic evaluations, the results may not be generalizable beyond the perspective of analysis.
Association between entero‐hepatic Helicobacter species and Crohn’s disease: a prospective cross‐sectional study
Authors: LAHARIE D. , ASENCIO C. , ASSELINEAU J. , BULOIS P. , BOURREILLE A. , MOREAU J. , BONJEAN P. , LAMARQUE D. , PARIENTE A. , SOULÉ J.‐C. , CHARACHON A. , COFFIN B. , PEREZ P. , MÉGRAUD F. , ZERBIB F.
Published: May 2009

Background  The pathogenesis of Crohn’s disease (CD) involved microbial factors. Some Helicobacter species, the so‐called entero‐hepatic Helicobacters (EHH), can naturally colonize the intestinal surface and have been detected in humans.

Aim  To look for an association between CD and the presence of EHH DNA in intestinal biopsies.

Methods  Two groups of patients were included prospectively in a multicentre cross‐sectional study: CD patients with an endoscopic post‐operative recurrence within 2 years following a surgical resection and controls screened for colorectal polyps or cancer. Intestinal biopsies were taken for Helicobacter culture and Helicobacter 16S DNA detection. If positive, the EHH species were identified with specific PCRs, sequencing and denaturing gradient gel electrophoresis.

Results  In the 165 included patients (73 CD and 92 controls), Helicobacter cultures were negative. PCR was positive in 44% of CD and 47% of controls. After age‐adjustment, CD was significantly associated with EHH in intestinal biopsies (OR = 2.58; 95%CI: 1.04–6.67). All EHH species detected were identified as Helicobacter pullorum and the closely related species Helicobacter canadensis.

Conclusion  Crohn’s disease is associated with the presence of EHH species DNA in intestinal biopsies after adjustment for age. Whether these species play a role in the pathophysiology of CD remains to be determined.
QTL for resistance to Salmonella carrier state confirmed in both experimental and commercial chicken lines
Authors: Calenge F. , Lecerf F. , Demars J. , Feve K. , Vignoles F. , Pitel F. , Vignal A. , Velge P. , Sellier N. , Beaumont C.
Published: May 2009

The ability of chickens to carry Salmonella without displaying disease symptoms is responsible for Salmonella propagation in poultry stocks and for subsequent human contamination through the consumption of contaminated eggs or meat. The selection of animals more resistant to carrier state might be a way to decrease the propagation of Salmonella in poultry stocks and its transmission to humans. Five QTL controlling variation for resistance to carrier state in a chicken F2 progeny derived from the White Leghorn inbred lines N and 61 had been previously identified using a selective genotyping approach. Here, a second analysis on the whole progeny was performed, which led to the confirmation of two QTL on chromosomes 2 and 16. To assess the utility of these genomic regions for selection in commercial lines, we tested them together with other QTL identified in an [N×61] × N backcross progeny and with the candidate genes SLC11A1 and TLR4. We used a commercial line divergently selected for either low or high carrier‐state resistance both in young chicks and in adult hens. In divergent chick lines, one QTL on chromosome 1 and one in the SLC11A1 region were significantly associated with carrier‐state resistance variations; in divergent adult lines, one QTL located in the major histocompatibility complex on chromosome 16 and one in the SLC11A1 region were involved in these variations. Genetic studies conducted on experimental lines can therefore be of potential interest for marker‐assisted selection in commercial lines.
Trajectory analysis of the lower Brent Group (Jurassic), Northern North Sea: contrasting depositional patterns during the advance of a major deltaic system
Authors: Bullimore S. A. , Helland‐Hansen W.
Published: May 2009

Trajectory analysis is an alternative approach to systems tract analysis in unravelling the sequence stratigraphic development of sedimentary successions. Whereas the latter anticipates a succession of the depositional history in terms of a given order of systems tracts, trajectory analysis combines trajectory classes in any order, thus providing a more flexible interpretation of the depositional evolution with fewer a priori assumptions about the type or the nature of the mechanisms driving sequence development. The overall regressive part of the Brent Delta (Middle Jurassic, Northern North Sea) has been analysed using this approach. The distribution, thicknesses and stacking patterns of facies associations have been analysed to unravel the trajectorial behaviour of the system. In proximal areas (Oseberg domain), thin shoreface/foreshore packages associated with a prograding strandplain are overlain by upper delta‐plain (floodplain) and distributary channel deposits. Flat or descending regressive trajectories can explain the stratigraphic development in this area. A short distance to the north (Huldra domain), the presence of thicker shoreface/foreshore packages and lower delta‐plain sediments suggests a low‐angle ascending regressive trajectory. In more distal areas (Gullfaks and Visund domains), a higher rate of aggradation leads to the development of even thicker shoreface/foreshore packages and the development of lagoons and bays in the lower delta‐plain realm. Alternating high‐ and low‐angle ascending regressive trajectories can explain the distal development.
Non‐invasive measurement of the haemodynamic effects of inhaled salbutamol, intravenous L‐arginine and sublingual nitroglycerin
Authors: Tahvanainen Anna , Leskinen Miia , Koskela Jenni , Ilveskoski Erkki , Alanko Juha , Kähönen Mika , Kööbi Tiit , Lehtimäki Lauri , Moilanen Eeva , Mustonen Jukka , Pörsti Ilkka
Published: May 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Haemodynamic effects of endothelial stimuli induced by salbutamol and L‐arginine in humans have been previously studied predominantly at rest in selected vascular beds.

• We studied the effects of salbutamol, L‐arginine and nitroglycerin on cardiac and vascular function by continuous recording of pulse wave analysis and impedance cardiography both in the supine position and during passive head‐up tilt.

WHAT THIS STUDY ADDS

• The divergent effects of the research drugs in supine position and during head‐up tilt indicate that human haemodynamics should also be studied in the upright position.

• Since inhaled salbutamol induced more pronounced changes in haemodynamics, it provides a clinically more applicable tool than infused L‐arginine for the assessment of endothelial function in humans.

AIMS

To examine the effects of salbutamol and L‐arginine, two compounds acting largely on the endothelium, and the endothelium‐independent agent nitroglycerin on blood pressure, arterial compliance, cardiac function and vascular resistance.

METHODS

Continuous radial pulse wave analysis, whole‐body impedance cardiography, and plethysmographic blood pressure from fingers in the supine position and during head‐up tilt were recorded in nine healthy subjects. Data were captured before and after L‐arginine (10 mg mg−1 min−1) or saline infusion, salbutamol (400 µg) or placebo inhalation, and sublingual nitroglycerin (0.25 mg) or placebo resoriblet.

RESULTS

The results of all measurements were comparable before drug administration. The effects of inhaled salbutamol were apparent in the supine position: systemic vascular resistance (−9.2 ± 2.6%) and augmentation index (−4.0 ± 1.5%) decreased, and heart rate (8.6 ± 2.5%) and cardiac output (8.8 ± 3.1%) increased. L‐arginine had no clear effects on supine haemodynamics, but during head‐up tilt blood pressure was moderately decreased and reduction in aortic reflection time prevented, indicating improved large arterial compliance. Nitroglycerin reduced supine vascular resistance (−6.7 ± 1.8%) and augmentation index (−7.4 ± 1.6%), and increased cardiac output (+9.2 ± 2.7%). During head‐up tilt, nitroglycerin increased cardiac output (+10.6 ± 5.6%) and heart rate (+40 ± 7.5%), decreased vascular resistance (−7.8 ± 5.8%) and augmentation index (−18.7 ± 3.2%), and prevented the decrease in aortic reflection time.

CONCLUSIONS

Inhaled salbutamol predominantly changed supine haemodynamics, whereas the moderate effects of L‐arginine were observed during the head‐up tilt. In contrast, small doses of nitroglycerin induced major changes in haemodynamics both supine and during the head‐up tilt. Altogether, these results emphasize the importance of haemodynamic measurements in both the supine and upright positions.
Cranberry juice suppressed the diclofenac metabolism by human liver microsomes, but not in healthy human subjects
Authors: Ushijima Kentarou , Tsuruoka Shu‐ichi , Tsuda Hidetoshi , Hasegawa Gohki , Obi Yuri , Kaneda Tae , Takahashi Masaki , Maekawa Tomohiro , Sasaki Tomohiro , Koshimizu Taka‐aki , Fujimura Akio
Published: May 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Cranberry juice has a significant inhibitory effect on CYP2C9 activity in vitro, whereas it shows a minimal effect on the pharmacokinetics and pharmacodynamics of warfarin, a CYP2C9 substrate in vivo.

• Information regarding the interaction between cranberry juice and other medications metabolized by CYP2C9 is limited.

WHAT THIS STUDY ADDS

• Cranberry juice suppressed the metabolism of diclofenac, another CYP2C9 substrate, by human liver microsomes.

• Pharmacokinetic parameters of diclofenac were not altered by cranberry juice consumption in human subjects.

AIM

To investigate a potential interaction between cranberry juice and diclofenac, a substrate of CYP2C9.

METHODS

The inhibitory effect of cranberry juice on diclofenac metabolism was determined using human liver microsome assay. Subsequently, we performed a clinical trial in healthy human subjects to determine whether the repeated consumption of cranberry juice changed the diclofenac pharmacokinetics.

RESULTS

Cranberry juice significantly suppressed diclofenac metabolism by human liver microsomes. On the other hand, repeated consumption of cranberry juice did not influence the diclofenac pharmacokinetics in human subjects.

CONCLUSIONS

Cranberry juice inhibited diclofenac metabolism by human liver microsomes, but not in human subjects. Based on the present and previous findings, we think that although cranberry juice inhibits CYP2C9 activity in vitro, it does not change the pharmacokinetics of medications metabolized by CYP2C9 in clinical situations.
Communicating benefit and risk
Authors: Baglin Trevor
Published: May 2009

Improved reporting of clinical trials and greater engagement by patients in treatment decisions requires that clinicians have a working knowledge of estimates of benefit and risk and how to communicate these measures. A basic understanding of study design and analysis is often neglected by clinicians in training, and recent analyses indicate that inadequate reporting and design are associated with biassed estimates of treatment effects. Communicating likely treatment results to patients requires presentation of information as absolute rather than relative risk, using common denominators or probabilities, and explaining risk with reference to a proposed treatment duration. Conveying uncertainty in relation to estimates of likelihood is particularly difficult when discussing outcomes with patients and often the clinician is still left with phrases such as ‘best guess’.
The prognosis of clinical monoclonal B cell lymphocytosis differs from prognosis of Rai 0 chronic lymphocytic leukaemia and is recapitulated by biological risk factors
Authors: Rossi Davide , Sozzi Elisa , Puma Alessia , De Paoli Lorenzo , Rasi Silvia , Spina Valeria , Gozzetti Alessandro , Tassi Maristella , Cencini Emanuele , Raspadori Donatella , Pinto Valeria , Bertoni Francesco , Gattei Valter , Lauria Francesco , Gaidano Gianluca , Forconi Francesco
Published: May 2009

Monoclonal B‐cell lymphocytosis (MBL) is an asymptomatic monoclonal expansion of <5·0 × 109/l circulating CLL‐phenotype B‐cells. The relationship between MBL and Rai 0 CLL, as well as the impact of biological risk factors on MBL prognosis, are unknown. Out of 460 B‐cell expansions with CLL‐phenotype, 123 clinical MBL (cMBL) were compared to 154 Rai 0 CLL according to clinical and biological profile and outcome. cMBL had better humoral immune capacity and lower infection risk, lower prevalence of del11q22‐q23/del17p13 andTP53mutations, slower lymphocyte doubling time, and longer treatment‐free survival. Also, cMBL diagnosis was a protective factor for treatment risk. Despite these favourable features, all cMBL were projected to progress, and lymphocytes <1·2 × 109/l and >3·7 × 109/l were the best thresholds predicting the lowest and highest risk of progression to CLL. AlthoughIGHVstatus, CD38 and CD49d expression, and fluorescencein situhybridization (FISH) karyotype individually predicted treatment‐free survival, multivariate analysis identified the presence of +12 or del17p13 as the sole independent predictor of treatment requirement in cMBL (Hazard ratio: 5·39, 95% confidence interval 1·98–14·44,P = 0·001). Overall, these data showed that cMBL has a more favourable clinical course than Rai 0 CLL. Given that the biological profile can predict treatment requirement, stratification based on biological prognosticators may be helpful for cMBL management.
Treatment of adults with BCR‐ABL negative acute lymphoblastic leukaemia with a modified paediatric regimen
Authors: Storring John M. , Minden Mark D. , Kao Susan , Gupta Vikas , Schuh Andre C. , Schimmer Aaron D. , Yee Karen W. L. , Kamel‐Reid Suzanne , Chang Hong , Lipton Jeffrey H. , Messner Hans A. , Xu Wei , Brandwein Joseph M.
Published: May 2009

Between 2000 and 2006, 85 adult BCR‐ABL negative acute lymphoblastic leukaemia (ALL) patients between 18 and 60 years of age were treated using a modified paediatric regimen, which included high doses of asparaginase delivered weekly for 30 weeks during intensification. The complete response rate with induction therapy was 89%, and decreased with increasing age, mainly due to higher induction mortality. All post‐induction treatments were delivered on an outpatient basis. The most common complications during intensification were infections (47%), osteonecrosis (32%), venous thromboembolism (23%) and neuropathy (22%). At a median follow‐up of 4 years, the 5‐year overall survival (OS) and relapse‐free survival (RFS) were 63% and 71%, respectively. Significant adverse predictors for OS were age >35 years, high white blood cell count, MLL rearrangement, allogeneic stem cell transplantation in first complete remission and <80% of the planned asparaginase dose delivered during intensification. Patients aged ≤35 years had a 3 year OS of 83%, as compared to 52% for patients aged >35 years. We conclude that the administration of this paediatric regimen is feasible and has considerable activity in adult ALL, particularly in younger patients. Effective delivery of asparaginase dosing appears to be important in achieving an optimal antileukaemic effect.
Marked downregulation of the granulopoiesis regulator LEF1 is associated with disease progression in the myelodysplastic syndromes
Authors: Pellagatti Andrea , Marafioti Teresa , Paterson Jennifer C. , Malcovati Luca , Della Porta Matteo G. , Jädersten Martin , Pushkaran Beena , George Tracy I. , Arber Daniel A. , Killick Sally , Giagounidis Aristoteles , Hellström‐Lindberg Eva , Cazzola Mario , Wainscoat James S. , Boultwood Jacqueline
Published: May 2009

Lymphoid enhancer‐binding factor 1 (LEF1) is a neutrophilic granulopoiesis regulator whose absence is critical in congenital neutropenia. We have shown LEF1 downregulation in the CD34+ cells of the majority of myelodysplastic syndromes (MDS) patients. LEF1 was the most significant differentially expressed gene between early and advanced MDS. Marked LEF1 downregulation was found in 27/32 patients with advanced MDS and in 6/35 patients with early MDS, and was associated with neutropenia. Downregulation of LEF1 mRNA was reflected at the protein level. Immunostaining for CD34/LEF1 may represent a marker of advanced MDS. LEF1 may play a role in the defective maturation of myeloid progenitors in MDS.
Highly increased familial risks for specific lymphoma subtypes
Authors: Goldin Lynn R. , Björkholm Magnus , Kristinsson Sigurdur Y. , Turesson Ingemar , Landgren Ola
Published: May 2009

Studies have shown that familial risk contributes to aetiology of lymphomas. Using large population registries from Sweden, we evaluated risk of lymphoma subtypes among first‐degree relatives of 2668 follicular lymphoma (FL) patients, 2517 diffuse large B‐cell lymphoma (DLBCL) patients, and 6963 Hodgkin lymphoma (HL) patients compared to first‐degree relatives of controls. Relatives were at the highest risk for developing the same lymphoma subtype as the case. DLBCL was increased 10‐fold among relatives of DLBCL patients, FL was increased fourfold among relatives of FL patients and HL was increased fourfold among relatives of HL patients. These results imply that germline susceptibility genes are specific to lymphoma subtype.
Influence of water flow velocity, water depth and colony distance on distribution and foraging patterns of terns in the Wadden Sea
Authors: SCHWEMMER PHILIPP , ADLER SVEN , GUSE NILS , MARKONES NELE , GARTHE STEFAN
Published: May 2009

Surface‐feeding seabirds, such as Common (Sterna hirundo) and Arctic Terns (Sterna paradisaea) in the German Wadden Sea, are dependent on biological and physical processes that affect prey availability close to the water surface. We proposed the following four hypotheses: (i) relationships should exist between high water flow velocity and foraging activity of terns, as turbulence should enhance prey availability at the surface; (ii) the areas of highest foraging success should be located within areas of low water depth, due to enhanced biological productivity; (iii) as terns are known to have small foraging radii, the location of their breeding grounds should be related to the location of their foraging grounds; (iv) terns should forage intensely in river estuaries, as these should hold ample food supplies. The time between terns leaving the colony and their first foraging attempt differed significantly among different tidal stages: the time was shortest during flood and ebb tides (i.e., highest water flow velocities). Modelling of a long‐term data set revealed the highest probability of foraging activity in conditions of high water currents, in both shallow areas and in areas of around 15–20 m depth. Foraging activity was negatively correlated with distance from colony. The distance to the closest estuary had no significant effect on foraging behaviour. Our findings emphasize the physical–biological coupling in the Wadden Sea and highlight the overall importance of small‐scale physical processes in directly influencing prey availability for surface‐feeding seabirds.
Sensitivity analysis of sea scallop (Placopecten magellanicus) larvae trajectories to hydrodynamic model configuration on Georges Bank and adjacent coastal regions
Authors: TIAN RUCHENG C. , CHEN CHANGSHENG , STOKESBURY KEVIN D. E. , ROTHSCHILD BRIAN J. , XU QICHUN , HU SONG , COWLES GEOFFREY , HARRIS BRADLEY P. , MARINO II MICHAEL C.
Published: May 2009

The previous larval‐trajectory modeling studies on Georges Bank were assessed through process‐oriented Lagrangian‐tracking comparison experiments using the high‐resolution Gulf of Maine/Georges Bank Finite‐Volume Coastal Ocean Model (GOM‐FVCOM). The results indicate that in a strong nonlinear system such as Georges Bank, the passive tracer movement is driven by a fully three‐dimensional Lagrangian flow field that varies in space and time due to large tidal excursion and steep bottom topography. The particle‐tracking methods developed based on the assumption of weak nonlinearity of the flow field are not applicable to Georges Bank. The results of previous larval transport studies driven by circulation fields constructed under the weak‐nonlinearity assumption need to be interpreted with caution. In the present work, the influence of model physical setups on sea scallop larval dispersal and settlement on Georges Bank and adjacent shelf regions is examined. Distinct differences in the spatial distribution of the passive larvae predicted by the model under various physical conditions suggest that a fully nonlinear model driven by realistic spatially and temporally varying forcing should be employed for Lagrangian‐based studies of fishery population dynamics on Georges Bank.
Separating physical disturbance and nutrient enrichment caused by Pacific salmon in stream ecosystems
Authors: TIEGS SCOTT D. , CAMPBELL EMILY Y. , LEVI PETER S. , RÜEGG JANINE , BENBOW MARK E. , CHALONER DOMINIC T. , MERRITT RICHARD W. , TANK JENNIFER L. , LAMBERTI GARY A.
Published: May 2009

1. Pacific salmon (Oncorhynchus spp.) deliver marine‐derived nutrients to the streams in which they spawn and die, and these resource subsidies can increase the abundance of stream biota. In strong contrast, physical disturbance from salmon spawning activity can reduce the abundance of benthic organisms. Previous experimental designs have not established the relative effects of these two contrasting processes on stream organisms during a salmon run.

2. We combined manipulative and observational field studies to assess the degree of nutrient enrichment, physical disturbance, and the net effect of salmon on the abundance of benthic periphyton. Related salmon‐mediated processes were also evaluated for benthic macroinvertebrates. Mesh exclosures (2 × 2 m plots) prevented salmon from disturbing areas of the stream channel, which were compared with areas to which salmon had access. Sampling was conducted both before and during the late‐summer spawning run of pink (O. gorbushca) and chum (O. keta) salmon.

3. Streamwater nitrogen and phosphorus concentrations increased sharply with the onset of the salmon run, and highly significant positive relationships were observed between the numbers of salmon present in the stream and these dissolved nutrients. Before the salmon run, periphyton biomass (as chlorophyll a) and total macroinvertebrate abundance were very similar between control and exclosure plots. During the salmon run, exclosures departed substantially from controls, suggesting significant disturbance imparted on benthic biota.

4. Comparing exclosures before and during the salmon run enabled us to estimate the effects of salmon in the absence of direct salmon disturbance. This ‘nutrient enrichment potential’ was significant for periphyton biomass, as was a related index for macroinvertebrate abundance (although enhanced invertebrate drift into exclosures during the salmon run could also have been important). Interestingly, however, the net effect of salmon, evaluated by comparing control plots before and during the salmon run, was relatively modest for both periphyton and macroinvertebrates, suggesting that nutrient enrichment effects were largely offset by disturbance.

5. Our results illustrate the importance of isolating the specific mechanisms via which organisms affect ecosystems, and indicate that the relative magnitude of salmon nutrient enrichment and benthic disturbance determines the net effect that these ecologically important fish have on stream ecosystems.
Artificial drainage and associated carbon fluxes (CO2/CH4) in a tundra ecosystem
Authors: MERBOLD L. , KUTSCH W. L. , CORRADI C. , KOLLE O. , REBMANN C. , STOY P. C. , ZIMOV S. A. , SCHULZE E.‐D.
Published: May 2009

Ecosystem flux measurements using the eddy covariance (EC) technique were undertaken in 4 subsequent years during summer for a total of 562 days in an arctic wet tundra ecosystem, located near Cherskii, Far‐Eastern Federal District, Russia. Methane (CH4) emissions were measured using permanent chambers. The experimental field is characterized by late thawing of permafrost soils in June and periodic spring floods. A stagnant water table below the grass canopy is fed by melting of the active layer of permafrost and by flood water. Following 3 years of EC measurements, the site was drained by building a 3 m wide drainage channel surrounding the EC tower to examine possible future effects of global change on the tundra tussock ecosystem. Cumulative summertime net carbon fluxes before experimental alteration were estimated to be about +15 g C m−2 (i.e. an ecosystem C loss) and +8 g C m−2 after draining the study site. When taking CH4 as another important greenhouse gas into account and considering the global warming potential (GWP) of CH4 vs. CO2, the ecosystem had a positive GWP during all summers. However CH4 emissions after drainage decreased significantly and therefore the carbon related greenhouse gas flux was much smaller than beforehand (475 ± 253 g C‐CO2‐e m−2 before drainage in 2003 vs. 23 ± 26 g C‐CO2‐e m−2 after drainage in 2005).
Differential gene expression during compensatory sprouting of dendrites in the auditory system of the cricketGryllus bimaculatus
Authors: Horch H. W. , McCarthy S. S. , Johansen S. L. , Harris J. M.
Published: May 2009

Neurones that lose their presynaptic partners because of injury usually retract or die. However, when the auditory interneurones of the cricketGryllus bimaculatusare denervated, dendrites respond by growing across the midline and forming novel synapses with the opposite auditory afferents. Suppression subtractive hybridization was used to detect transcriptional changes 3 days after denervation. This is a stage at which we demonstrate robust compensatory dendritic sprouting. Whereas 49 unique candidates were down‐regulated, no sufficiently up‐regulated candidates were identified at this time point. Several candidates identified in this study are known to influence the translation and degradation of proteins in other systems. The potential role of these factors in the compensatory sprouting of cricket auditory interneurones in response to denervation is discussed.
XPC gene polymorphisms and risk of idiopathic azoospermia or oligozoospermia in a Chinese population
Authors: Liang Jie , Gu Aihua , Xia Yankai , Wu Bin , Lu Ningxia , Wang Wei , Lu Chuncheng , Zheng Qian , Wang Shoulin , Wang Xinru
Published: May 2009

A retrospective case–control study was carried out in the Han‐Chinese population to determine the polymorphisms of xeroderma pigmentosum complementation group C (XPC) gene on the risk of idiopathic azoospermia or oligozoospermia. The Ala499Val (C>T) and Lys939Gln (A>C) polymorphism of XPC gene were genotyped by polymerase chain reaction‐restriction fragment length polymorphism in three groups of infertile men (172 patients of azoospermia, 25 patients of severe oligozoospermia, 55 patients of oligozoospermia) and 228 fertile men. Increased risk of idiopathic azoospermia, but not oligozoospermia was associated with the XPC variant genotypes of Ala499Val (C>T) [adjusted odds ratio (OR) = 1.67, 95% confidence interval (CI) = 1.04–2.68 for CT heterozygote and adjusted OR = 2.03, 95% CI = 1.10–3.75 for TT homozygote] compared with CC homozygous wide‐type. The Lys939Gln (A>C) polymorphism was not related to spermatogenic failure. The combined risk alleles analysis and haplotype analysis showed that ORs increased as the number of the risk alleles increased and the 499T‐939C haplotype had a significantly increased risk of idiopathic azoospermia (OR = 7.97; 95% CI = 3.51–18.07) compared with other haplotypes. The results suggest that XPC Ala499Val (C>T) polymorphism is correlated with high risk of idiopathic azoospermia in the Han‐Chinese population.
The long pentraxin 3 is a soluble and cell‐associated component of the human semen
Authors: Doni Andrea , Paffoni Alessio , Nebuloni Manuela , Ragni Guido , Pasqualini Fabio , Valentino Sonia , Bonetti Silvia , Mantovani Alberto , Somigliana Edgardo , Garlanda Cecilia
Published: May 2009

The long pentraxin 3 (PTX3) is a multifunctional soluble pattern recognition receptor, involved in several processes ranging from innate resistance and inflammation to clearance of apoptotic cells and organization of hyaluronic acid‐rich extracellular matrices. PTX3 is also a novel marker in several pathological conditions of infectious, inflammatory, or autoimmune origin. This study was designed to assess whether PTX3 is expressed in the male reproductive tract and whether PTX3 interacts with human spermatozoa influencing their function. Here we show for the first time by immunohistochemistry that PTX3 is expressed in the male genital tract in perivascular connective tissue, in endothelial cells, in the interstitium, and in the cytoplasm of prostatic epithelial glandular cells; PTX3 was detectable in seminal plasma in variable levels, which correlated with the percentage of normal spermatozoa. Moreover, PTX3 binds to spermatozoa, in particular with immotile cells, localizing in the neck and in the subacrosomial region. Finally, recombinant PTX3 did not interfere with sperm motility.