bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence ofBartonellainfection in cats and dogs in a metropolitan area, Thailand
Authors: INOUE K. , MARUYAMA S. , KABEYA H. , KAWANAMI K. , YANAI K. , JITCHUM S. , JITTAPARAPONG S.
Published: April 2009

The prevalence ofBartonellainfection was studied in 312 cats and 350 dogs in the Bangkok metropolitan areas, Thailand, between June 2001 and February 2003.Bartonellawas isolated from 47 (16·3%) of 288 stray cats, but from none of the 24 pet cats studied. Of the 47Bartonella-positive cats, 45 animals were infected with onlyB. henselae, one was infected with onlyB. clarridgeiae, and one with bothB. henselaeandB. clarridgeiae. 16S rRNA typing showed that 40 cats were infected withB. henselaetype I, four withB. henselaetype II, and one with bothB. henselaetypes I and II. These results indicated thatB. henselae, especially type I, was prevalent in stray cats that constituted a largeBartonellareservoir in Bangkok.B. clarridgeiaewas isolated for the first time in Asia from one of 350 dogs.
Comparison of the prevalence of bacterial enteropathogens, potentially zoonotic bacteria and bacterial resistance to antimicrobials in organic and conventional poultry, swine and beef production: a systematic review and meta-analysis
Authors: YOUNG I. , RAJIĆ A. , WILHELM B. J. , WADDELL L. , PARKER S. , McEWEN S. A.
Published: April 2009

The prevalences of zoonotic and potentially zoonotic bacteria or bacteria resistant to antimicrobials in organic and conventional poultry, swine and beef production were compared using systematic review and meta-analysis methodology. Thirty-eight articles were included in the review. The prevalence of Campylobacter was higher in organic broiler chickens at slaughter, but no difference in prevalence was observed in retail chicken. Campylobacter isolates from conventional retail chicken were more likely to be ciprofloxacin-resistant (odds ratio 9·62, 95% confidence interval 5·67–16·35). Bacteria isolated from conventional animal production exhibited a higher prevalence of resistance to antimicrobials; however, the recovery of some resistant strains was also identified in organic animal production, where there is an apparent reduced antimicrobial selection pressure. Limited or inconsistent research was identified in studies examining the prevalence of zoonotic and potentially zoonotic bacteria in other food-animal species. There is a need for further research of sufficient quality in this area.
Food intake and prevalence of obesity in Brazil: an ecological analysis
Authors: Lobato Jackeline Christiane Pinto , Costa Antonio José Leal , Sichieri Rosely
Published: April 2009

Objective

To investigate the correlation between the consumption of refined carbohydrates and fats and the prevalence of obesity in the state capitals of Brazil.

Design

An ecological evaluation of obesity and dietary risk factors was carried out in twenty-six state capitals of Brazil.

Setting

Analysis was based on the age-standardized prevalence of obesity (BMI ≥ 30·0 kg/m2) among adults aged 20–59 years. Both intake and obesity prevalence were obtained from the last National Family Household Budget Survey (HBS). The survey was conducted from July 2002 to June 2003, based on a probabilistic national sample of 48 470 households. In each household, during seven consecutive days, all monetary and non-monetary expenses for food and beverages for family consumption were transformed into energy. The relative contribution of foods and food groups was expressed as the proportion (%) of total energy. Fruits and vegetables were also measured by the quantity bought in grams.

Results

Prevalence of obesity varied from 5·1 % to 13·6 % among women and from 5·2 % to 17·6 % among men. For women, there were statistically significant correlations between obesity and intake of sugar and soft drinks (rS = 0·60; P = 0·001), ready-to-eat meals (rS = 0·39; P = 0·05) and potatoes (rS = 0·40; P = 0·04). For men there were no such associations.

Conclusions

Increasing intake of refined carbohydrates, mainly soft drinks, may play a role in the prevalence of obesity among women in Brazil. Effecting changes in family purchase patterns may be a strategy to reduce obesity.
Scytonemin: molecular structural studies of a key extremophilic biomarker for astrobiology
Authors: Varnali Tereza , Edwards Howell G.M. , Hargreaves Michael D.
Published: April 2009

Ab initio calculations for scytonemin, an important ultraviolet (UV)-radiation protective biomolecule synthesized by extremophilic cyanobacteria in stressed terrestrial environments, are reported for the first time. Vibrational spectroscopic assignments for the previously studied Raman spectra assist in the identification of the major features in the observed data. Calculations of the electronic absorption spectra confirm the capability of this molecule to absorb in all three regions of the UV, UVA, UVB and UVC, and also illustrate the need for a dimeric species in this respect. The presence of significant steric hindrance between the two halves of the dimeric molecule about the C—C bridging bond in scytonemin forces the molecule significantly out of planarity, contrary to assumptions made in the literature; however, it appears that the monomer is capable of absorbing to only a limited extent in the UVB and UVC regions only, so conferring a special emphasis upon the need for the dimerization to remove the lower-energy UV radiation whilst still affording protection for the chlorophyll with transmission of the visible radiation required for photosynthesis. The observation of vibrational band wavenumber coincidences for the first time between the infrared and Raman spectra confirm the non-planar structural prediction from the calculations. The results of this study provide information about the protective chemical strategies of terrestrial extremophilic cyanobacteria and provide a basis for the search for molecules of this type in the astrobiological exploration of Mars.
A magnetotelluric survey in the Northern Bolivian Altiplano
Authors: Ritz Michel , Bondoux Francis , Hérail Gérard , Sempéré Thomas
Published: April 2009

Magnetotelluric (MT) measurements were performed at 9 sites on the northern Bolivian Altiplano in a attempt to determine thicknesses of the Cainozoic sedimentary infill and to characterize the underlying crust. At some of the sites the MT soundings show complications due to static shift effects caused by local, surficial heterogeneities. Preliminary one‐dimensional (ID) modeling of the data based on the impedance tensor determinant parameters was undertaken for sites considered to be free of static effects, and was followed by 2D modeling. The model obtained indicates, from the surface downward, three important geoelectrical units, namely (1) a very low‐resistivity layer (1–6 ohm‐ m) consisting of Late Cainozoic volcanic rocks and/or Tertiary‐Cretaceous sedimentary rocks 1–4 km in thickness, (2) a crustal resistive zone (about 200 ohm‐m), and (3) a lower crustal or uppermost mantle conductor (less than 10 ohm‐m) at depths of 40–45 km which might be related to partial melting. This model is consistent with the geological model according to which the Altiplano formed as a synorogenic basin showing abrupt changes in depositional thicknesses across thrust faults.
SemanticSBML: a tool for annotating, checking, and merging of biochemical models in SBML format
Authors: Liebermeister Wolfram , Krause Falko , Uhlendorf Jannis , Lubitz Timo , Klipp Edda
Published: April 2009

Semantic annotations in SBML (systems biology markup language) enable computer programs to check and process biochemical models based on their biochemical meaning. Annotations are an important prerequisite for model merging, which would be a major step towards the construction of large-scale cell models. The software tool semanticSBML allows users to check and edit MIRIAM annotations and SBO terms, the most common forms of annotation in SBML models. It uses a large collection of biochemical names and database identifiers to support modellers in finding the right annotations. Annotated SBML models can also be built from lists of chemical reactions. In model merging, semanticSBML suggests a preliminary merged model based on MIRIAM annotations in the original models. This model provides a starting point for manually aligning the elements of all input models. To resolve conflicting element properties, conflicts are highlighted and categorised. The user can navigate through the models, change the matching of model elements, check the conflicts between them and decide how they should be resolved. Alternatively, the software can resolve all conflicts automatically, selecting each time the attribute value from the input model with highest priority.URL: "http://www.semanticsbml.org/":http://www.semanticsbml.org/
The role of Havana and communities in the manual curation of unfinished vertebrate genomes
Authors: Carvalho-Silva Denise , Chen Chao-Kung , Frankish Adam , Gilbert James , Gordon Leo , Hunt Toby , Larbaoui Mustapha , Loveland Jane , Mudge Jonathan , Sehra Harminder , Snow Catherine , Steward Charlie , Suner Marie Marthe , Thomas Mark , Wilming Laurens , Harrow Jennifer
Published: April 2009

Manual annotation‭ (‬the‭ "‬museum‭" ‬model of annotation‭) ‬relies on a small group of specialized curators to catalogue and classify genes according to their functional roles.‭ This‬ is both costly and time consuming and therefore is used only for model organisms with sufficient funding.‭ ‬Smaller research communities often have to rely on other models of annotation,‭ ‬mainly automated annotation‭ (‬the‭ "‬factory‭" ‬model,‭ ‬e.g.‭ ‬Ensembl‭)‬,‭ ‬and the‭ "‬jamboree‭" ‬model‭ (‬in which a group of leading biologists from the community and bioinformaticians come together for a short intensive annotation workshop‭)‬.‭ ‬At the Wellcome Trust Sanger Institute‭ (‬WTSI‭)‬,‭ ‬the Havana team provides high quality manual annotation of finished vertebrate genome sequences,‭ ‬namely human,‭ ‬mouse and zebrafish.‭ ‬We also perform the curation of specific finished regions such as the MHC in dog,‭ ‬cow and pig,‭ ‬whose whole genomes have been‭ ‬assembled from unfinished BACs or from whole genome shotgun sequences.‭ ‬In addition,‭ ‬we at Havana have also hosted annotation jamborees for the cow‭ (‬Bos taurus‭) ‬and pig‭ (‬Sus scrofa‭) ‬genomes.‭ ‬During those sessions,‭ ‬the research community had the opportunity to annotate their genes of interest under expert guidance using the custom written publicly available Otterlace annotation system,‭ ‬and the unified manual annotation guidelines.‭ ‬By making use of the tools and skills acquired during the cow and pig jamborees,‭ ‬the delegates can continue annotating their genomes remotely.‭ ‬For the pig genome,‭ ‬a highly contiguous physical map has been generated by an international effort of four laboratories (available in Pre!Ensembl) and‭ ‬is being used as a substrate for the swine genome sequencing project.‭ ‬Upcoming vertebrate genomes will be sequenced to a high depth coverage with the next generation sequencing technologies‭ (‬e.g.‭ ‬Illumina,‭ ‬454,‭ ‬SOLiD‭) ‬but will have the drawback of not being manually finished.‭ ‬Manual annotation will be more accurate than the automated predictions at coping with any assembly problems derived from these high coverage but unfinished‭ (‬or automatic pre-finished‭) ‬genomes.‭ ‬Once these inherent assembly errors are corrected and the gene structures are accurately identified with manual annotation,‭ ‬the curated genes will be incorporated and merged with the predicted gene models in Ensembl to provide a unified view of the landscape of vertebrate genomes.‭ ‬I will present an introduction to our manual annotation system and our experience using it for annotation jamborees at the WTSI.
Group III secreted phospholipase A2 transgenic mice spontaneously develop inflammation
Authors: Sato Hiroyasu , Taketomi Yoshitaka , Isogai Yuki , Masuda Seiko , Kobayashi Tetsuyuki , Yamamoto Kei , Murakami Makoto
Published: April 2009

PLA2 (phospholipase A2) group III is an atypical sPLA2 (secretory PLA2) that is homologous with bee venom PLA2 rather than with other mammalian sPLA2s. In the present paper, we show that endogenous group III sPLA2 (PLA2G3) is expressed in mouse skin and that Tg (transgenic) mice overexpressing human PLA2G3 spontaneously develop skin inflammation. Pla2g3-Tg mice over 9 months of age frequently developed dermatitis with hyperkeratosis, acanthosis, parakeratosis, erosion, ulcer and sebaceous gland hyperplasia. The dermatitis was accompanied by infiltration of neutrophils and macrophages and by elevated levels of pro-inflammatory cytokines, chemokines and prostaglandin E2. In addition, Pla2g3-Tg mice had increased lymph aggregates and mucus in the airway, lymphocytic sialadenitis, hepatic extramedullary haemopoiesis, splenomegaly with increased populations of granulocytes and monocytes/macrophages, and increased serum IgG1. Collectively, these observations provide the first demonstration of spontaneous development of inflammation in mice with Tg overexpression of mammalian sPLA2.
Inhibition of myeloperoxidase-mediated hypochlorous acid production by nitroxides
Authors: Rees Martin D. , Bottle Steven E. , Fairfull-Smith Kathryn E. , Malle Ernst , Whitelock John M. , Davies Michael J.
Published: April 2009

Tissue damage resulting from the extracellular production of HOCl (hypochlorous acid) by the MPO (myeloperoxidase)-hydrogen peroxide-chloride system of activated phagocytes is implicated as a key event in the progression of a number of human inflammatory diseases. Consequently, there is considerable interest in the development of therapeutically useful MPO inhibitors. Nitroxides are well established antioxidant compounds of low toxicity that can attenuate oxidative damage in animal models of inflammatory disease. They are believed to exert protective effects principally by acting as superoxide dismutase mimetics or radical scavengers. However, we show here that nitroxides can also potently inhibit MPO-mediated HOCl production, with the nitroxide 4-aminoTEMPO inhibiting HOCl production by MPO and by neutrophils with IC50 values of approx. 1 and 6 μM respectively. Structure–activity relationships were determined for a range of aliphatic and aromatic nitroxides, and inhibition of oxidative damage to two biologically-important protein targets (albumin and perlecan) are demonstrated. Inhibition was shown to involve one-electron oxidation of the nitroxides by the compound I form of MPO and accumulation of compound II. Haem destruction was also observed with some nitroxides. Inhibition of neutrophil HOCl production by nitroxides was antagonized by neutrophil-derived superoxide, with this attributed to superoxide-mediated reduction of compound II. This effect was marginal with 4-aminoTEMPO, probably due to the efficient superoxide dismutase-mimetic activity of this nitroxide. Overall, these data indicate that nitroxides have considerable promise as therapeutic agents for the inhibition of MPO-mediated damage in inflammatory diseases.
Long QT syndrome and associated gene mutation carriers in Japanese children: results from ECG screening examinations
Authors: Hayashi Kenshi , Fujino Noboru , Uchiyama Katsuharu , Ino Hidekazu , Sakata Kenji , Konno Tetsuo , Masuta Eiichi , Funada Akira , Sakamoto Yuichiro , Tsubokawa Toshinari , Nakashima Keisuke , Liu Li , Higashida Haruhiro , Hiramaru Yoshitake , Shimizu Masami , Yamagishi Masakazu
Published: April 2009

LQTS (long QT syndrome) is caused by mutations in cardiac ion channel genes; however, the prevalence of LQTS in the general population is not well known. In the present study, we prospectively estimated the prevalence of LQTS and analysed the associated mutation carriers in Japanese children. ECGs were recorded from 7961 Japanese school children (4044 males; mean age, 9.9±3.0 years). ECGs were examined again for children who had prolonged QTc (corrected QT) intervals in the initial ECGs, and their QT intervals were measured manually. An LQTS score was determined according to Schwartz's criteria, and ion channel genes were analysed. In vitro characterization of the identified mutants was performed by heterologous expression experiments. Three subjects were assigned to a high probability of LQTS (3.5≤ LQTS score), and eight subjects to an intermediate probability (1.0< LQTS score ≤3.0). Genetic analysis of these II subjects identified three KCNH2 mutations (M124T, 547–553 del GGCGGCG and 2311–2332 del/ins TC). In contrast, no mutations were identified in the 15 subjects with a low probability of LQTS. Electrophysiological studies showed that both the M124T and the 547–553 del GGCGGCG KCNH2 did not suppress the wild-type KCNH2 channel in a dominant-negative manner. These results demonstrate that, in a random sample of healthy Japanese children, the prevalence of a high probability of LQTS is 0.038% (three in 7961), and that LQTS mutation carriers can be identified in at least 0.038% (one in 2653). Furthermore, large-scale genetic studies will be needed to clarify the real prevalence of LQTS by gene-carrier status, as it may have been underestimated in the present study.
Angiotensin-(1–7), an alternative metabolite of the renin–angiotensin system, is up-regulated in human liver disease and has antifibrotic activity in the bile-duct-ligated rat
Authors: Lubel John S. , Herath Chandana B. , Tchongue Jorge , Grace Josephine , Jia Zhiyuan , Spencer Karen , Casley David , Crowley Peter , Sievert William , Burrell Louise M. , Angus Peter W.
Published: April 2009

Ang-(1–7) (angiotensin-1–7), a peptide product of the recently described ACE (angiotensin-converting enzyme) homologue ACE2, opposes the harmful actions of AngII (angiotensin II) in cardiovascular tissues, but its role in liver disease is unknown. The aim of the present study was to assess plasma levels of Ang-(1–7) in human liver disease and determine its effects in experimental liver fibrosis. Angiotensin peptide levels were measured in cirrhotic and non-cirrhotic patients with hepatitis C. The effects of Ang-(1–7) on experimental fibrosis were determined using the rat BDL (bile-duct ligation) model. Liver histology, hydroxyproline quantification and expression of fibrosis-related genes were assessed. Expression of RAS (renin–angiotensin system) components and the effects of Ang-(1–7) were examined in rat HSCs (hepatic stellate cells). In human patients with cirrhosis, both plasma Ang-(1–7) and AngII concentrations were markedly elevated (P<0.001). Non-cirrhotic patients with hepatitis C had elevated Ang-(1–7) levels compared with controls (P<0.05), but AngII concentrations were not increased. In BDL rats, Ang-(1–7) improved fibrosis stage and collagen Picrosirius Red staining, and reduced hydroxyproline content, together with decreased gene expression of collagen 1A1, α-SMA (smooth muscle actin), VEGF (vascular endothelial growth factor), CTGF (connective tissue growth factor), ACE and mas [the Ang-(1–7) receptor]. Cultured HSCs expressed AT1Rs (AngII type 1 receptors) and mas receptors and, when treated with Ang-(1–7) or the mas receptor agonist AVE 0991, produced less α-SMA and hydroxyproline, an effect reversed by the mas receptor antagonist A779. In conclusion, Ang-(1–7) is up-regulated in human liver disease and has antifibrotic actions in a rat model of cirrhosis. The ACE2/Ang-(1–7)/mas receptor axis represents a potential target for antifibrotic therapy in humans.
Effects of androgens on endothelial progenitor cellsin vitroandin vivo
Authors: Fadini Gian Paolo , Albiero Mattia , Cignarella Andrea , Bolego Chiara , Pinna Christian , Boscaro Elisa , Pagnin Elisa , De Toni Renzo , De Kreutzenberg Saula , Agostini Carlo , Avogaro Angelo
Published: April 2009

The beneficial or detrimental effects of androgens on the cardiovascular system are debated. Endothelial progenitor cells are bone-marrow-derived cells involved in endothelial healing and angiogenesis, which promote cardiovascular health. Oestrogens are potent stimulators of endothelial progenitor cells, and previous findings have indicated that androgens may improve the biology of these cells as well. In the present study, we show that testosterone and its active metabolite dihydrotestosterone exert no effects on the expansion and function of late endothelial progenitors isolated from the peripheral blood of healthy human adult males, whereas they positively modulate early ‘monocytic’ endothelial progenitor cells. In parallel, we show that castration in rats is followed by a decrease in circulating endothelial progenitor cells, but that testosterone and dihydrotestosterone replacement fails to restore endothelial progenitor cells towards normal levels. This is associated with persistently low oestrogen levels after androgen replacement in castrated rats. In a sample of 62 healthy middle-aged men, we show that circulating endothelial progenitor cell levels are more directly associated with oestradiol, rather than with testosterone, concentrations. In conclusion, our results collectively demonstrate that androgens exert no direct effects on endothelial progenitor cell biology in vitro and in vivo.
A Re-Examination of the Factors That Influence Productivity in Hotels: A Study of the Housekeeping Function
Authors: Jones Peter , Siag Abhijeet
Published: April 2009

Evidence from a number of studies suggests that productivity in hotels is largely driven by factors outside the control of the manager. This paper questions this assumption by examining the level of productivity in the housekeeping departments in a chain of 45 hotels. The paper reviews the concept of productivity and the issues relating to its measurement, before reviewing previous studies of productivity in the hotel sector. A number of factors are identified that appear to affect productivity performance. These are then investigated through analysing one year's data from a web-based labour scheduling system that records every hour worked by every employee in a chain of hotels. This kind of data has not been used in any previous published study, which unlike studies based on Data Envelopment Analysis, enables specific performance indices or benchmarks to be identified. The paper concludes that there is no significant difference in productivity levels according to the size, location, demand variability or age of the hotel, thereby refuting evidence from some prior studies. It concludes that managers have much more control over productivity performance than previously thought.
Comparison of the Efficacy of a Hydrogen Peroxide Dry-Mist Disinfection System and Sodium Hypochlorite Solution for Eradication ofClostridium difficileSpores
Authors: Barbut F. , Menuet D. , Verachten M. , Girou E.
Published: April 2009

Objective.

To compare a hydrogen peroxide dry-mist system and a 0.5% hypochlorite solution with respect to their ability to disinfectClostridiumdifficile-contaminated surfaces in vitro and in situ.

Design.

Prospective, randomized, before-after trial.

Setting.

Two French hospitals affected byC. difficile.

Intervention.

In situ efficacy of disinfectants was assessed in rooms that had housed patients withC. difficileinfection. A prospective study was performed at 2 hospitals that involved randomization of disinfection processes. When a patient withC. difficileinfection was discharged, environmental contamination in the patient's room was evaluated before and after disinfection. Environmental surfaces were sampled forC. difficileby use of moistened swabs; swab samples were cultured on selective plates and in broth. Both disinfectants were tested in vitro with a spore-carrier test; in this test, 2 types of material, vinyl polychloride (representative of the room's floor) and laminate (representative of the room's furniture), were experimentally contaminated with spores from 3C. difficilestrains, including the epidemic clone ribotype 027-North American pulsed-field gel electrophoresis type 1.

Results.

There were 748 surface samples collected (360 from rooms treated with hydrogen peroxide and 388 from rooms treated with hypochlorite). Before disinfection, 46 (24%) of 194 samples obtained in the rooms randomized to hypochlorite treatment and 34 (19%) of 180 samples obtained in the rooms randomized to hydrogen peroxide treatment showed environmental contamination. After disinfection, 23 (12%) of 194 samples from hypochlorite-treated rooms and 4 (2%) of 180 samples from hydrogen peroxide treated rooms showed environmental contamination, a decrease in contamination of 50% after hypochlorite decontamination and 91% after hydrogen peroxide decontamination (P< .005). The in vitro activity of 0.5% hypochlorite was time dependent. The mean (±SD) reduction in initial log10 bacterial count was 4.32 ± 0.35 log10 colony-forming units after 10 minutes of exposure to hypochlorite and 4.18 ± 0.8 logl0 colony-forming units after 1 cycle of hydrogen peroxide decontamination.

Conclusion.

In situ experiments indicate that the hydrogen peroxide dry-mist disinfection system is significantly more effective than 0.5% sodium hypochlorite solution at eradicating Сdifficilespores and might represent a new alternative for disinfecting the rooms of patients withC. difficileinfection.
Outbreak of Pseudomonas aeruginosa Infection Associated With Contamination of a Flexible Bronchoscope
Authors: DiazGranados Carlos A. , Jones Marolyn Y. , Kongphet-Tran Thiphasone , White Nancy , Shapiro Mark , Wang Yun F. , Ray Susan M. , Blumberg Henry M.
Published: April 2009

Background.

A cluster of patients with respiratory cultures positive for Pseudomonas aeruginosa with a unique antibiogram was observed during June and July 2007 at a 1,000-bed urban teaching hospital in Atlanta, Georgia. These P. aeruginosa isolates were recovered from bronchoscopically obtained specimens.

Methods.

A cross-sectional study was performed to assess whether the cluster was associated with exposure to a particular bronchoscope (B1); cultures from specimens from the bronchoscopes and the environment were obtained, and the P. aeruginosa isolate type was determined using pulsed-field gel electrophoresis (PFGE). Records of patients exposed to B1 during the cluster period were reviewed.

Results.

Twelve patients with a culture positive for P. aeruginosa with the unique susceptibility pattern were identified in June-July 2007. No cases were documented from March 1 through May 31, 2007. Culture specimens obtained from B1 after high-level disinfection revealed P. aeruginosa, prompting removal of B1 from service on July 23, 2007. No cases occurred after that date. Eleven (55%) of 20 patients who were exposed to Bl during the cluster period had a culture positive for P. aeruginosa, compared with 1 (2%) of 53 patients who were exposed to other bronchoscopes (P < .001). PFGE patterns for P. aeruginosa isolates obtained from case patients and from B1 were identical. An engineering evaluation of B1 documented several internal damages. Two (10.5%) of 19 patients exposed to Bl during the cluster period may have developed P. aeruginosa infection following exposure to B1.

Conclusions.

An outbreak or pseudo-outbreak of P. aeruginosa infection occurred in association with use of a damaged bronchoscope. Periodic engineering maintenance may be needed to prevent bronchoscope contamination that is resistant to high-level disinfection.
BEsTRF: a tool for optimal resolution of terminal-restriction fragment length polymorphism analysis based on user-defined primer–enzyme–sequence databases
Authors: Stres Blaž , Tiedje James M. , Murovec Boštjan
Published: April 2009

Summary: BEsTRF (Best Estimated T-RF) provides a standalone environment for analyzing primers-enzymes-gene section combinations used in terminal-restriction fragment length polymorphism (T-RFLP) for its optimal resolution. User-defined sequence databases of several hundred thousand DNA sequences can be explored and the resolution of user-specified sets of primers and restriction endonucleases can be analyzed on either forward or reverse terminal fragments. Sequence quality, primer mismatches, insertions and deletions can be controlled and each primer pair-specific sequence collections can be exported for downstream analyses. The configuration for a novel T-RFLP population profiling using rpoB gene (DNA-directed RNA polymerase, beta subunit) on forward fluorescently labeled primer are presented.

Availability: BEsTRF is freely available at http://lie.fe.uni-lj.si/bestrf and can be downloaded from the same site. The online protocol, numerous primer and enzyme dictionaries, sequence collections and results generated during this work for various genes are available at our website http://lie.fe.uni-lj.si/bestrf.

Contact:  blaz.stres@bfro.uni-lj.si
Variations in the target strength of Atlantic cod during vertical migration
Authors: Rose George A.
Published: April 2009

Rose, G. A. 2009. Variations in the target strength of Atlantic cod during vertical migration. – ICES Journal of Marine Science, 66: 1205–1211. Experiments conducted at sea in June 1999 and January 2000 indicated that the mean target strength (TS) of Atlantic cod (Gadus morhua) varies not just with length, but also with pressure (depth) and fish orientation, particularly during vertical migration. In June, when fish were migrating and spawning, vertical migration was pronounced, extending up to 150 m off the seabed, and the associated TS declined by as much as 5 dB. In January, when the fish were located nearer the seabed, mean TS was more stable and matched a conventional model of TS vs. length [L, cm; i.e. TS = 20 log(L) − 66] based on measurements of ex situ fish orientated horizontally and positioned at close range. This paper demonstrates that mean TS is inversely related (p < 0.05) to the range off the seabed (r, m), which includes 90% of fish. Based on this finding, a new multivariate TS model is proposed: TS = 20 log(L) − 65 − 0.05 r. In this model, r is a proxy for swimbladder volume and fish orientation. A survey in May 2007 found that cod (mean L = 63 cm) dispersed in such a way that single targets could be resolved up to 100 m from the seabed. Measurements of TS of in situ individual fish (TSindividual) and mean TS inferred from a comparison of area-backscattering coefficients (sa) and count-based densities (TSindirect) were positively correlated with a slope not different from unity. Means of these TS estimates were −32.4 and −32.2 dB, respectively, or ∼2.3 dB less than that predicted by the conventional model. In contrast, the new multivariate model predicts TS = −32.5 dB, which is nearly identical with the means of TSindividual and TSindirect.
The acoustic quantification of fish in the presence of methane bubbles in the stratified Lake Kinneret, Israel
Authors: Ostrovsky Ilia
Published: April 2009

Ostrovsky, I. 2009. The acoustic quantification of fish in the presence of methane bubbles in the stratified Lake Kinneret, Israel. – ICES Journal of Marine Science, 66: 1043–1047. Methane ebullition from bottom sediments is common in many productive bodies of water. During acoustic surveys, the methane bubbles can be mistaken as fish. In the stratified Lake Kinneret, the densities and target-strength (TS) values of acoustic targets were measured with a 120-kHz, dual-beam echosounder at night, when the fish schools were dispersed and single targets could be detected. The density and TS of methane bubbles were estimated in the anoxic hypolimnion, where there were no fish. A discrete-bubble model was applied in combination with a TS vs. methane bubble-size relationship to estimate the methane bubble TS at different depths. This information was used to quantify the densities of methane bubbles and fish, and the fish TS in the epilimnion where both types of target were found. During periods of rapid decrease in water level, methane bubbles could be the principal acoustic targets in the epilimnion, and their TS strongly overlapped that of fish. In some strata, they contributed up to 90–95% of all targets. The amount of methane bubbles in the water column depends on the type of sediment, bottom depth, and the history of sediment degassing. Their presence could be a serious obstacle to the accurate assessment of fish abundance in lakes and reservoirs with varying water levels, where intensive gas emission is a common feature. For such situations, backscattering by methane bubbles must be taken into account to avoid the erroneous quantification of fish abundance.
Cellular Open Resource(COR): current status and future directions
Authors: Garny Alan , Noble Denis , Hunter Peter J. , Kohl Peter
Published: April 2009

The need for tools to aid the description and sharing of biological models was highlighted at the launch of the International Union of Physiological Sciences Physiome Project in 1997. This has resulted in the release, in 2001, of the CellML specifications (http://www.cellml.org/specifications/).Cellular Open Resource(COR) was among the early adopters of this standard, eventually forming the first publicly available CellML-based modelling and collaboration environment. From the onset, COR was designed to provide an environment that could not only be used by experienced modellers, but also by experimentalists, teachers and students. It therefore tries to combine a user-friendly interface with a computationally efficient numerical engine. In this paper, we introduce the philosophy behind COR, explain its user interface and current functionality, including the editing and running of CellML files, highlight lessons learned from user feedback and problems experienced during the development of COR and conclude by exploring future development potential.
In silicobiology of bone modelling and remodelling: regeneration
Authors: Geris L. , Vander Sloten J. , Van Oosterwyck H.
Published: April 2009

Bone regeneration is the process whereby bone is able to (scarlessly) repair itself from trauma, such as fractures or implant placement. Despite extensive experimental research, many of the mechanisms involved still remain to be elucidated. Over the last decade, many mathematical models have been established to investigate the regeneration processin silico. The first models considered only the influence of the mechanical environment as a regulator of the healing process. These models were followed by the development of bioregulatory models where mechanics was neglected and regeneration was regulated only by biological stimuli such as growth factors. The most recent mathematical models couple the influences of both biological and mechanical stimuli. Examples are given to illustrate the added value of mathematical regeneration research, specifically in thein silicodesign of treatment strategies for non-unions. Drawbacks of the current continuum-type models, together with possible solutions in extending the models towards other time and length scales are discussed. Finally, the demands for dedicated and more quantitative experimental research are presented.
A physiome standards-based model publication paradigm
Authors: Nickerson David P. , Buist Martin L.
Published: April 2009

In this era of widespread broadband Internet penetration and powerful Web browsers on most desktops, a shift in the publication paradigm for physiome-style models is envisaged. No longer will model authors simply submit an essentially textural description of the development and behaviour of their model. Rather, they will submit a complete working implementation of the model encoded and annotated according to the various standards adopted by the physiome project, accompanied by a traditional human-readable summary of the key scientific goals and outcomes of the work. While the final published, peer-reviewed article will look little different to the reader, in this new paradigm, both reviewers and readers will be able to interact with, use and extend the models in ways that are not currently possible. Here, we review recent developments that are laying the foundations for this new model publication paradigm. Initial developments have focused on the publication of mathematical models of cellular electrophysiology, using technology based on a CellML- or Systems Biology Markup Language (SBML)-encoded implementation of the mathematical models. Here, we review the current state of the art and what needs to be done before such a model publication becomes commonplace.
In silico
biology of bone modelling and remodelling: adaptation
Authors: Gerhard Friederike A. , Webster Duncan J. , van Lenthe G. Harry , Müller Ralph
Published: April 2009

Modelling and remodelling are the processes by which bone adapts its shape and internal structure to external influences. However, the cellular mechanisms triggering osteoclastic resorption and osteoblastic formation are still unknown. In order to investigate current biological theories,
in silico
models can be applied. In the past, most of these models were based on the continuum assumption, but some questions related to bone adaptation can be addressed better by models incorporating the trabecular microstructure. In this paper, existing simulation models are reviewed and one of the microstructural models is extended to test the hypothesis that bone adaptation can be simulated without particular knowledge of the local strain distribution in the bone. Validation using an experimental murine loading model showed that this is possible. Furthermore, the experimental model revealed that bone formation cannot be attributed only to an increase in trabecular thickness but also to structural reorganization including the growth of new trabeculae. How these new trabeculae arise is still an unresolved issue and might be better addressed by incorporating other levels of hierarchy, especially the cellular level. The cellular level sheds light on the activity and interplay between the different cell types, leading to the effective change in the whole bone. For this reason, hierarchical multi-scale simulations might help in the future to better understand the biomathematical laws behind bone adaptation.
Multi-level patient-specific modelling of the proximal femur. A promising tool to quantify the effect of osteoporosis treatment
Authors: Lenaerts Leen , van Lenthe G. Harry
Published: April 2009

Preventing femoral fractures is an important goal in osteoporosis research. In order to evaluate a person's fracture risk and to quantify response to treatment, bone competence is best assessed by bone strength. Finite-element (FE) modelling based on medical imaging is considered a very promising technique for the assessment ofin vivofemoral bone strength. Over the past decades, a number of different FE models have been presented focusing on the effect of several methodological aspects, such as mesh type, material properties and loading conditions, on the precision and accuracy of these models. In this paper, a review of this work is presented. We conclude that moderate to good predictions can be made, especially when the models are tuned to specific loading scenarios. However, there is room for improvement when multiple loading conditions need to be evaluated. We hypothesize that including anisotropic material properties is the first target. As a proof of the concept, we demonstrate that the main orientation of the femoral bone structure can be calculated from clinical computed tomography scans. We hypothesize that this structural information can be used to estimate the anisotropic bone material properties, and that in the future this could potentially lead to a greater predictive value of FE models for femoral bone strength.
Robust modelling, measurement and analysis of human and animal metabolic systems
Authors: van Beek Johannes H.G.M. , Hauschild Anne-Christin , Hettling Hannes , Binsl Thomas W.
Published: April 2009

Modelling human and animal metabolism is impeded by the lack of accurate quantitative parameters and the large number of biochemical reactions. This problem may be tackled by: (i) study of modules of the network independently; (ii) ensemble simulations to explore many plausible parameter combinations; (iii) analysis of ‘sloppy’ parameter behaviour, revealing interdependent parameter combinations with little influence; (iv) multiscale analysis that combines molecular and whole network data; and (v) measuring metabolic flux (rate of flow)
in vivo
via stable isotope labelling. For the latter method, carbon transition networks were modelled with systems of ordinary differential equations, but we show that coloured Petri nets provide a more intuitive graphical approach. Analysis of parameter sensitivities shows that only a few parameter combinations have a large effect on predictions. Model analysis of high-energy phosphate transport indicates that membrane permeability, inaccurately known at the organellar level, can be well determined from whole-organ responses. Ensemble simulations that take into account the imprecision of measured molecular parameters contradict the popular hypothesis that high-energy phosphate transport in heart muscle is mostly by phosphocreatine. Combining modular, multiscale, ensemble and sloppy modelling approaches with
in vivo
flux measurements may prove indispensable for the modelling of the large human metabolic system.
Numerical solution of the bidomain equations
Authors: Linge S. , Sundnes J. , Hanslien M. , Lines G.T. , Tveito A.
Published: April 2009

Knowledge of cardiac electrophysiology is efficiently formulated in terms of mathematical models. However, most of these models are very complex and thus defeat direct mathematical reasoning founded on classical and analytical considerations. This is particularly so for the celebrated bidomain model that was developed almost 40 years ago for the concurrent analysis of extra- and intracellular electrical activity. Numerical simulations based on this model represent an indispensable tool for studying electrophysiology. However, complex mathematical models, steep gradients in the solutions and complicated geometries lead to extremely challenging computational problems. The greatest achievement in scientific computing over the past 50 years has been to enable the solving of linear systems of algebraic equations that arise from discretizations of partial differential equations in an optimal manner, i.e. such that the central processing unit (CPU) effort increases linearly with the number of computational nodes. Over the past decade, such optimal methods have been introduced in the simulation of electrophysiology. This development, together with the development of affordable parallel computers, has enabled the solution of the bidomain model combined with accurate cellular models, on geometries resembling a human heart. However, in spite of recent progress, the full potential of modern computational methods has yet to be exploited for the solution of the bidomain model. This paper reviews the development of numerical methods for solving the bidomain model. However, the field is huge and we thus restrict our focus to developments that have been made since the year 2000.
C
haste
: incorporating a novel multi-scale spatial and temporal algorithm into a large-scale open source library
Authors: Bernabeu Miguel O. , Bordas Rafel , Pathmanathan Pras , Pitt-Francis Joe , Cooper Jonathan , Garny Alan , Gavaghan David J. , Rodriguez Blanca , Southern James A. , Whiteley Jonathan P.
Published: April 2009

Recent work has described the software engineering and computational infrastructure that has been set up as part of the Cancer, Heart and Soft Tissue Environment (C
haste
) project. C
haste
is an open source software package that currently has heart and cancer modelling functionality. This software has been written using a programming paradigm imported from the commercial sector and has resulted in a code that has been subject to a far more rigorous testing procedure than that is usual in this field. In this paper, we explain how new functionality may be incorporated into C
haste
. Whiteley has developed a numerical algorithm for solving the bidomain equations that uses the multi-scale (MS) nature of the physiology modelled to enhance computational efficiency. Using a simple geometry in two dimensions and a purpose-built code, this algorithm was reported to give an increase in computational efficiency of more than two orders of magnitude. In this paper, we begin by reviewing numerical methods currently in use for solving the bidomain equations, explaining how these methods may be developed to use the MS algorithm discussed above. We then demonstrate the use of this algorithm within the C
haste
framework for solving the monodomain and bidomain equations in a three-dimensional realistic heart geometry. Finally, we discuss how C
haste
may be developed to include new physiological functionality—such as modelling a beating heart and fluid flow in the heart—and how new algorithms aimed at increasing the efficiency of the code may be incorporated.
CellML metadata standards, associated tools and repositories
Authors: Beard Daniel A. , Britten Randall , Cooling Mike T. , Garny Alan , Halstead Matt D.B. , Hunter Peter J. , Lawson James , Lloyd Catherine M. , Marsh Justin , Miller Andrew , Nickerson David P. , Nielsen Poul M.F. , Nomura Taishin , Subramanium Shankar , Wimalaratne Sarala M. , Yu Tommy
Published: April 2009

The development of standards for encoding mathematical models is an important component of model building and model sharing among scientists interested in understanding multi-scale physiological processes. CellML provides such a standard, particularly for models based on biophysical mechanisms, and a substantial number of models are now available in the CellML Model Repository. However, there is an urgent need to extend the current CellML metadata standard to provide biological and biophysical annotation of the models in order to facilitate model sharing, automated model reduction and connection to biological databases. This paper gives a broad overview of a number of new developments on CellML metadata and provides links to further methodological details available from the CellML website.
Computer-aided design and finite-element modelling of biomaterial scaffolds for bone tissue engineering
Authors: Lacroix Damien , Planell Josep A. , Prendergast Patrick J.
Published: April 2009

Scaffold biomaterials for tissue engineering can be produced in many different ways depending on the applications and the materials used. Most research into new biomaterials is based on an experimental trial-and-error approach that limits the possibility of making many variations to a single material and studying its interaction with its surroundings. Instead, computer simulation applied to tissue engineering can offer a more exhaustive approach to test and screen out biomaterials. In this paper, a review of the current approach in biomaterials designed through computer-aided design (CAD) and through finite-element modelling is given. First we review the approach used in tissue engineering in the development of scaffolds and the interactions existing between biomaterials, cells and mechanical stimuli. Then, scaffold fabrication through CAD is presented and characterization of existing scaffolds through computed images is reviewed. Several case studies of finite-element studies in tissue engineering show the usefulness of computer simulations in determining the mechanical environment of cells when seeded into a scaffold and the proper design of the geometry and stiffness of the scaffold. This creates a need for more advanced studies that include aspects of mechanobiology in tissue engineering in order to be able to predict over time the growth and differentiation of tissues within scaffolds. Finally, current perspectives indicate that more efforts need to be put into the development of such advanced studies, with the removal of technical limitations such as computer power and the inclusion of more accurate biological and genetic processes into the developed algorithms.