Quantifying the Consistency of Scientific Databases

Science is a social process with far-reaching impact on our modern society. In recent years, for the first time we are able to scientifically study the science itself. This is enabled by massive amounts of data on scientific publications that is increasingly becoming available. The data is contained in several databases such as Web of Science or PubMed, maintained by various public and private entities. Unfortunately, these databases are not always consistent, which considerably hinders this study. Relying on the powerful framework of complex networks, we conduct a systematic analysis of the consistency among six major scientific databases. We found that identifying a single "best" database is far from easy. Nevertheless, our results indicate appreciable differences in mutual consistency of different databases, which we interpret as recipes for future bibliometric studies.     

Primary Amine Oxidase of Escherichia coli Is a Metabolic Enzyme that Can Use a Human Leukocyte Molecule as a Substrate

Escherichia coli amine oxidase (ECAO), encoded by the tynA gene, catalyzes the oxidative deamination of aromatic amines into aldehydes through a well-established mechanism, but its exact biological role is unknown. We investigated the role of ECAO by screening environmental and human isolates for tynA and characterizing a tynA-deletion strain using microarray analysis and biochemical studies. The presence of tynA did not correlate with pathogenicity. In tynA+ Escherichia coli strains, ECAO enabled bacterial growth in phenylethylamine, and the resultant H₂O₂ was released into the growth medium. Some aminoglycoside antibiotics inhibited the enzymatic activity of ECAO, which could affect the growth of tynA+ bacteria. Our results suggest that tynA is a reserve gene used under stringent environmental conditions in which ECAO may, due to its production of H₂O₂, provide a growth advantage over other bacteria that are unable to manage high levels of this oxidant. In addition, ECAO, which resembles the human homolog hAOC3, is able to process an unknown substrate on human leukocytes.     

CMPF Does Not Associate with Impaired Glucose Metabolism in Individuals with Features of Metabolic Syndrome

Objective

3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) is a metabolite produced endogenously from dietary sources of furan fatty acids. The richest source of furan fatty acids in human diet is fish. CMPF was recently shown to be elevated in fasting plasma in individuals with gestational diabetes and type 2 diabetes, and mechanistically high level of CMPF was linked to β cell dysfunction. Here we aimed to study the association between plasma CMPF level and glucose metabolism in persons with impaired glucose metabolism.

Methods

Plasma CMPF concentration was measured from plasma samples of the study participants in an earlier controlled dietary intervention. All of them had impaired glucose metabolism and two other characteristics of the metabolic syndrome. Altogether 106 men and women were randomized into three groups for 12 weeks with different fish consumption (either three fatty fish meals per week, habitual fish consumption or maximum of one fish meal per week). Associations between concentration of CMPF and various glucose metabolism parameters at an oral glucose tolerance test at baseline and at the end of the study were studied.

Results

Fasting plasma CMPF concentration was significantly increased after a 12-week consumption of fatty fish three times per week, but the concentration remained much lower compared to concentrations reported in diabetic patients. Increases of plasma CMPF concentrations mostly due to increased fish consumption were not associated with impaired glucose metabolism in this study. Instead, elevated plasma CMPF concentration was associated with decreased 2-hour insulin concentration in OGTT.

Conclusions

Moderately elevated concentration of CMPF in plasma resulting from increased intake of fish is not harmful to glucose metabolism. Further studies are needed to fully explore the role of CMPF in the pathogenesis of impaired glucose metabolism.

Trial Registration

ClinicalTrials.gov NCT00573781     

Repair of DNA damage induced by the mycotoxin alternariol involves tyrosyl-DNA phosphodiesterase 1

Alternariol (AOH) was reported recently to act as a topoisomerase poison. To underline the relevance of topoisomerase targeting for the genotoxic properties of AOH, we addressed the question whether human tyrosyl-DNA phosphodiesterase 1 (TDP1), an enzyme vital to the repair of covalent DNA-topoisomerase adducts, affects AOH-mediated genotoxicity. The relevance of TDP1 activity on AOH-induced genotoxicity was investigated by the comet assay in human cells overexpressing GFP chimera of TDP1 or the inactive mutant TDP1^H263A as well as in cells subjected to siRNA-mediated knock-down of endogenous TDP1. Cells overexpressing TDP1 exhibited significantly less DNA damage after treatment with AOH in comparison to cells expressing the inactive mutant TDP1^H263A. In accordance with these results, levels of AOH inducing DNA strand breaks were increased in TDP1-suppressed cells in comparison to cells transfected with control siRNA. The specific topoisomerase poisons camptothecin and etoposide caused comparable effects, underlining that TDP1 plays an important role in the repair of topoisomerase-mediated DNA damage. In summary, the repair enzyme TDP1 was identified as a factor for the modulation of AOH-mediated DNA damage in human cells.     

The cluster-randomized Quality Initiative in Rectal Cancer trial: evaluating a quality-improvement strategy in surgery

Background

Following surgery for rectal cancer, two unfortunate outcomes for patients are permanent colostomy and local recurrence of cancer. We tested whether a quality-improvement strategy to change surgical practice would improve these outcomes.

Methods

Sixteen hospitals were cluster-randomized to the intervention (Quality Initiative in Rectal Cancer strategy) or control (normal practice) arm. Consecutive patients with primary rectal cancer were accrued from May 2002 to December 2004. Surgeons at hospitals in the intervention arm could voluntarily participate by attending workshops, using opinion leaders, inviting a study team surgeon to demonstrate optimal techniques of total mesorectal excision, completing postoperative questionnaires, and receiving audits and feedback. Main outcome measures were hospital rates of permanent colostomy and local recurrence of cancer.

Results

A total of 56 surgeons (n = 558 patients) participated in the intervention arm and 49 surgeons (n = 457 patients) in the control arm. The median follow-up of patients was 3.6 years. In the intervention arm, 70% of surgeons participated in workshops, 70% in intraoperative demonstrations and 71% in postoperative questionnaires. Surgeons who had an intraoperative demonstration provided care to 86% of the patients in the intervention arm. The rates of permanent colostomy were 39% in the intervention arm and 41% in the control arm (odds ratio [OR] 0.97, 95% confidence interval [CI] 0.63–1.48). The rates of local recurrence were 7% in the intervention arm and 6% in the control arm (OR 1.06, 95% CI 0.68–1.64).

Interpretation

Despite good participation by surgeons, the resource-intense quality-improvement strategy did not reduce hospital rates of permanent colostomy or local recurrence compared with usual practice. (ClinicalTrials.gov trial register no. {"type":"clinical-trial","attrs":{"text":"NCT00182130","term_id":"NCT00182130"}}NCT00182130.)Following surgery for rectal cancer, two unfortunate outcomes for patients are permanent colostomy and local recurrence of the cancer. Local recurrence is especially feared, because it is usually inoperable and patients can suffer a slow, painful death.¹ The use of total mesorectal excision, which involves dissection of the lymph node-bearing portion of the rectum,² has resulted in improved outcomes, with local recurrence rates as low as 1%–5% and rates of permanent colostomy of 10%–15%.^3–6 Population-based rates of local recurrence are unavailable for any North American jurisdiction, although a Canadian hospital series found that rates varied from 10% to 45% based on the practice volume and training of surgeons.⁷ A surgical report on health regions in the province of Ontario (population 13 million) found that rates of permanent colostomy varied from 31% to 41%.⁸ This geographic variation in outcomes, together with rates of inferior outcomes as compared to outcomes specific to total mesorectal excision, suggest that gaps exist in the quality of rectal surgery provided to patients with rectal cancer.Quality-improvement strategies for encouraging physicians to change practice include continuing medical education, the use of opinion leaders, and audit and feedback.^9–11 As well, improvement may be enhanced by using a participatory and supportive approach that focuses on the system and not on individual practitioners.^12,13 The small number of studies that have evaluated changes in surgeons’ practices often have targeted process measures, such as preoperative ordering of antibiotics, rather than patient outcomes, such as recurrence of cancer.^14,15We tested whether use of a surgeon-directed quality-improvement strategy would improve hospital rates of permanent colostomy and local recurrence of cancer among patients undergoing surgery for rectal cancer. We used the Quality Initiative in Rectal Cancer (QIRC) strategy, which integrates quality-improvement interventions and principles to encourage surgeons to provide optimal total mesorectal excision to patients with rectal cancer.¹⁶     

Laboratory Animal Management Assistant (LAMA): a LIMS for active research colonies

Laboratory Animal Management Assistant (LAMA) is an internet-based system for tracking large laboratory mouse colonies. It has a user-friendly interface with powerful search capabilities that ease day-to-day tasks such as tracking breeding cages and weaning litters. LAMA was originally developed to manage hundreds of new mouse strains generated by a large functional genomics program, the Pleiades Promoter Project (http://www.pleiades.org). The software system has proven to be highly flexible, suitable for diverse management approaches to mouse colonies. It allows custom tagging and grouping of animals, simplifying project-specific handling and access to data. Finally, LAMA was developed in close collaboration with mouse technicians to ease the transition from paper- or Excel-based management systems to computerized tracking, allowing data export in a popular spreadsheet format and automatic printing of cage cards. LAMA is an open-access software tool, freely available to the research community at http://launchpad.net/mousedb.     

Divergence genetics analysis reveals historical population genetic processes leading to contrasting phylogeographic patterns in co-distributed species

Coalescent samplers are computational time machines for inferring the historical demographic genetic processes that have given rise to observable patterns of spatial genetic variation among contemporary populations. We have used traditional characterizations of population structure and coalescent‐based inferences about demographic processes to reconstruct the population histories of two co‐distributed marine species, the frilled dog whelk, Nucella lamellosa, and the bat star, Patiria miniata. Analyses of population structure were consistent with previous work in both species except that additional samples of N. lamellosa showed a larger regional genetic break on Vancouver Island (VI) rather than between the southern Alexander Archipelago as in P. miniata. Our understanding of the causes, rather than just the patterns, of spatial genetic variation was dramatically improved by coalescent analyses that emphasized variation in population divergence times. Overall, gene flow was greater in bat stars (planktonic development) than snails (benthic development) but spatially homogeneous within species. In both species, these large phylogeographic breaks corresponded to relatively ancient divergence times between populations rather than regionally restricted gene flow. Although only N. lamellosa shows a large break on VI, population separation times on VI are congruent between species, suggesting a similar response to late Pleistocene ice sheet expansion. The absence of a phylogeographic break in P. miniata on VI can be attributed to greater gene flow and larger effective population size in this species. Such insights put the relative significance of gene flow into a more comprehensive historical biogeographic context and have important implications for conservation and landscape genetic studies that emphasize the role of contemporary gene flow and connectivity in shaping patterns of population differentiation.     

Quantification of lysophosphatidic acids in rat brain tissue by liquid chromatography–electrospray tandem mass spectrometry

Lysophosphatidic acid (LPA) is a lipid mediator with multiple biological functions. A highly selective and sensitive liquid chromatography–tandem mass spectrometry (LC/MS/MS) method was developed for the determination of LPAs (16:0 LPA, 18:0 LPA, 18:1 LPA, 20:4 LPA) in rat brain cryosections. After partitioning the LPAs from other lipophilic material present in the tissue with a liquid–liquid extraction, a reversed-phase column and ion pair technique was used for separating analytes with a gradient elution. An internal standard (17:0 LPA) was included in the analysis. Detection and quantification of the LPAs were carried out with a triple quadrupole mass spectrometer using negative electrospray ionization (ESI) and multiple reaction monitoring (MRM). The artificial formation of LPAs from lysophosphatidylcholines during the sample preparation procedure and instrumentation was carefully studied during the method development. The method was validated; acceptable selectivity, accuracy, precision, recovery, and stability were obtained for concentrations within the calibration curve range of 0.02–1.0 μM for LPAs. The quantification limit of the assay was 54 fmol injected into column for each LPAs. The method was applied to comparative studies of LPA levels in rat brain cryosections after the various chemical pre-treatments of the sections.     

Encapsulation of recombinant <Emphasis Type="Italic">E. coli</Emphasis> expressing cyclopentanone monooxygenase in polyelectrolyte complex capsules for Baeyer–Villiger biooxidation of 8-oxabicyclo[3.2.1]oct-6-en-3-one

Recombinant Escherichia coli cells, over-expressing cyclopentanone monooxygenase activity, were immobilized in polyelectrolyte complex capsules, made of sodium alginate, cellulose sulfate, poly(methylene-co-guanidine), CaCl₂ and NaCl. More than 90% of the cell viability was preserved during the encapsulation process. Moreover, the initial enzyme activity was fully maintained within encapsulated cells while it halved in free cells. Both encapsulated and free cells reached the end point of the Baeyer–Villiger biooxidation of 8-oxabicyclo[3.2.1]oct-6-en-3-one to 4,9-dioxabicyclo[4.2.1]non-7-en-3-one at the same time (48 h). Similarly, the enantiomeric excess above 94% was identical for encapsulated and free cells.