bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic and static deuterium inventory in ASDEX Upgrade with tungsten first wall
Authors: Rohde V. , Mayer M. , Mertens V. , Neu R. , Sugiyama K.
Published: July 2009

Hydrogen retention in the divertor tokamak ASDEX Upgrade is studied by surface analysis and gas balances methods. Comparing carbon and tungsten plasma facing components (PFCs), the deuterium content of deposits at the divertor plates has dropped by a factor of 13. With tungsten PFCs only 0.7% of the puffed hydrogen is retained, including a significant amount deeply implanted in the tungsten coatings at the outer divertor. Gas balances for ITER relevant high density H-mode discharges lead to a hydrogen retention averaged over a discharge of 8.2 ± 3.3% for tungsten PFCs and 23 ± 7% for carbon PFCs. For tungsten PFCs wall saturation is observed, i.e. only 1.5 ± 3.5% of the puffed gas is retained after reaching steady state conditions. Within the error bars all hydrogen outgasses within 15 min.
Magnetic order and confinement improvement in high-current regimes of RFX-mod with MHD feedback control
Authors: Piovesan P. , Zuin M. , Alfier A. , Bonfiglio D. , Bonomo F. , Canton A. , Cappello S. , Carraro L. , Cavazzana R. , Escande D.F. , Fassina A. , Gobbin M. , Lorenzini R. , Marrelli L. , Martin P. , Martines E. , Pasqualotto R. , Puiatti M.E. , Spolaore M. , Valisa M. , Vianello N. , Zanca P.
Published: July 2009

The RFX-mod machine (Sonato et al 2003 Fusion Eng. Des.
66 161) recently achieved, for the first time in a reversed-field pinch, high plasma current up to 1.6 MA with good confinement. Magnetic feedback control of magnetohydrodynamic instabilities was essential to reach the goal. As the current is raised, the plasma spontaneously accesses a new helical state, starting from turbulent multi-helical conditions. Together with this raise, the ratio between the dominant and the secondary mode amplitudes increases in a continuous way. This brings a significant improvement in the magnetic field topology, with the formation of helical flux surfaces in the core. As a consequence, strong helical transport barriers with maximum electron temperature around 1 keV develop in this region. The energy confinement time increases by a factor of 4 with respect to the lower-current, multi-helical conditions. The properties of the new helical state scale favourably with the current, thus opening promising perspectives for the higher current experiments planned for the near future.
Beneficial effects of statins after percutaneous coronary intervention
Authors: Zhang Zhi-Jiang , Marroquin Oscar C. , Weissfeld Joel L. , Stone Roslyn A. , Mulukutla Suresh R. , Williams David O. , Selzer Faith , Kip Kevin E.
Published: July 2009

Background

Evidence about the efficacy of statin treatment among patients after percutaneous coronary intervention (PCI) is very limited. The rapid advancement in PCI technology and near universal use of adjunctive cardioprotective medications make it necessary to formally assess the effect of statin therapy on cardiac events after PCI.

Design

This was a multicenter prospective cohort study.

Methods

Patients who received stent implantation and survived to hospital discharge from the National Heart, Lung, and Blood Institute Dynamic Registry from 2004 to 2006 formed the study cohort. Patients with cardiogenic shock, in-hospital adverse events [including myocardial infarction and coronary artery bypass graft surgery (CABG)], liver disease, renal disease, alcoholism, or drug abuse were excluded. The occurrences of death, CABG, and repeat PCI, and repeat revascularization were collected over 1-year follow-up.

Results

Of the 3227 patients evaluated, 2737 (85%) were prescribed a statin at discharge. By 1-year follow-up, incident events were 98 deaths, 44 CABG, 290 repeat PCI procedures, and 328 repeat revascularizations. After propensity score adjustment, postdischarge statin therapy was associated with lower risks of death [hazard ratio (HR): 0.58, 95% confidence interval (CI): 0.36–0.93, P = 0.02], CABG (HR: 0.49, 95% CI: 0.24–1.00, P = 0.05), and repeat revascularization (HR: 0.74, 95% CI: 0.56–1.00, P = 0.05).

Conclusion

These results support the routine use of statin therapy after PCI.
Development of genetic tools for in vivo virulence analysis of Streptococcus sanguinis
Authors: Senty Turner Lauren , Das Sankar , Kanamoto Taisei , Munro Cindy L. , Kitten Todd
Published: July 2009

Completion of the genome sequence of Streptococcus sanguinis SK36 necessitates tools for further characterization of this species. It is often desirable to insert antibiotic resistance markers and other exogenous genes into the chromosome; therefore, we sought to identify a chromosomal site for ectopic expression of foreign genes, and to verify that insertion into this site did not affect important cellular phenotypes. We designed three plasmid constructs for insertion of erm, aad9 or tetM resistance determinants into a genomic region encoding only a small (65 aa) hypothetical protein. To determine whether this insertion affected important cellular properties, SK36 and its erythromycin-resistant derivative, JFP36, were compared for: (i) growth in vitro, (ii) genetic competence, (iii) biofilm formation and (iv) virulence for endocarditis in the rabbit model of infective endocarditis (IE). The spectinomycin-resistant strain, JFP56, and tetracycline-resistant strain, JFP76, were also tested for virulence in vivo. Insertion of erm did not affect growth, competence or biofilm development of JFP36. Recovery of bacteria from heart valves of co-inoculated rabbits was similar to wild-type for JFP36, JFP56 and JFP76, indicating that IE virulence was not significantly affected. The capacity for mutant complementation in vivo was explored in an avirulent ssaB mutant background. Expression of ssaB from its predicted promoter in the target region restored IE virulence. Thus, the chromosomal site utilized is a good candidate for further manipulations of S. sanguinis. In addition, the resistant strains developed may be further applied as controls to facilitate screening for virulence factors in vivo.
Population structure of Streptococcus oralis
Authors: Do Thuy , Jolley Keith A. , Maiden Martin C. J. , Gilbert Steven C. , Clark Douglas , Wade William G. , Beighton David
Published: July 2009

Streptococcus oralisis a member of the normal human oral microbiota, capable of opportunistic pathogenicity; like related oral streptococci, it exhibits appreciable phenotypic and genetic variation. A multilocus sequence typing (MLST) scheme forS. oraliswas developed and the resultant data analysed to examine the population structure of the species. Analysis of 113 isolates, confirmed as belonging to theS. oralis/mitisgroup by 16S rRNA gene sequencing, characterized the population as highly diverse and undergoing inter- and intra-species recombination with a probable clonal complex structure. ClonalFrame analysis of theseS. oralisisolates along with examples ofStreptococcus pneumoniae,Streptococcus mitisandStreptococcus pseudopneumoniaegrouped the named species into distinct, coherent populations and did not support the clustering ofS. pseudopneumoniaewithS. mitisas reported previously using distance-based methods. Analysis of the individual loci suggested that this discrepancy was due to the possible hybrid nature ofS. pseudopneumoniae. The data are available on the public MLST website (http://pubmlst.org/soralis/).
Comparison of Bacteroides thetaiotaomicron and Escherichia coli 16S rRNA gene expression signals
Authors: Mastropaolo Matthew D. , Thorson Mary L. , Stevens Ann M.
Published: July 2009

There are barriers to cross-expression of genes betweenBacteroidesspp. andEscherichia coli. In this study, alux-based reporter system was developed forBacteroidesand used to compare the promoter structure and function of aBacteroides thetaiotaomicron4001 (BT4001) 16S rRNA promoter with those ofE. coli in vivo. Analysis of the BT4001 sequences upstream of the 16S rRNA gene revealed the same overall structure known forE. coli16S rRNA promoters in that there were two promoters separated by ∼150 bp. However, the BT4001 16S rRNA promoter contains the proposedBacteroides−7 and −33 consensus sequences instead of theE. coli−10 and −35 consensus sequences. The biological activity of various configurations of the BT4001 16S rRNA promoter was analysed. Experiments pairing the BT4001 16S rRNA promoter with anE. coliRBS, and vice-versa, confirmed that gene expression between the two species is restricted at the level of transcription. InBacteroides, a difference in translation initiation also appears to limit expression of foreign genes.
pH-dependent regulation of the multi-subunit cation/proton antiporter Pha1 system from Sinorhizobium meliloti
Authors: Yamaguchi Toshio , Tsutsumi Fuminori , Putnoky Péter , Fukuhara Masahiro , Nakamura Tatsunosuke
Published: July 2009

Thepha1gene cluster (pha1A′-G) ofSinorhizobium melilotihas previously been characterized as a necessary component for proper invasion into plant root tissue. It has been suggested to encode a multi-subunit K+/H+antiporter, since mutations in thepha1region renderedS. meliloticells sensitive to K+and alkali, and because there is high amino acid sequence similarity to previously characterized multi-subunit cation/H+antiporters (Mrp antiporters). However, the detailed transport properties of the Pha1 system are yet to be determined. Interestingly, most of the Mrp antiporters are highly selective for Na+, unlike the Pha1 system. Here, we report the functional expression of the Pha1 system inEscherichia coliand the measurement of cation/H+antiport activity. We showed that the Pha1 system is indeed a K+/H+antiporter with a pH optimum under mildly alkaline conditions. Moreover, we found that the Pha1 system can transport Na+; this was unexpected based on previous phenotypic analyses ofpha1mutants. Furthermore, we demonstrated that the cation selectivity of the Pha1 system was altered when the pH was lowered from the optimum. The downregulation of Na+/H+and K+/H+antiport activities upon acidic shift appeared to occur via different processes, which might indicate the presence of distinct mechanisms for the regulation of the K+/H+and Na+/H+antiport activities of the Pha1 system.
Detection and identification of specific bacteria in wound biofilms using peptide nucleic acid fluorescent in situ hybridization (PNA FISH)
Authors: Malic Sladjana , Hill Katja E. , Hayes Anthony , Percival Steven L. , Thomas David W. , Williams David W.
Published: July 2009

Biofilms provide a reservoir of potentially infectious micro-organisms that are resistant to antimicrobial agents, and their importance in the failure of medical devices and chronic inflammatory conditions is increasingly being recognized. Particular research interest exists in the association of biofilms with wound infection and non-healing, i.e. chronic wounds. In this study, fluorescent in situ hybridization (FISH) was used in combination with confocal laser scanning microscopy (CLSM) to detect and characterize the spatial distribution of biofilm-forming bacteria which predominate within human chronic skin wounds (Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus sp. and Micrococcus sp.). In vitro biofilms were prepared using a constant-depth film fermenter and a reconstituted human epidermis model. In vivo biofilms were also studied using biopsy samples from non-infected chronic venous leg ulcers. The specificity of peptide nucleic acid (PNA) probes for the target organisms was confirmed using mixed preparations of planktonic bacteria and multiplex PNA probing. Identification and location of individual bacterial species within multi-species biofilms demonstrated that P. aeruginosa was predominant. CLSM revealed clustering of individual species within mixed-species biofilms. FISH analysis of archive chronic wound biopsy sections showed bacterial presence and allowed bacterial load to be determined. The application of this standardized procedure makes available an assay for identification of single- or multi-species bacterial populations in tissue biopsies. The technique provides a reliable tool to study bacterial biofilm formation and offers an approach to assess targeted biofilm disruption strategies in vivo.
Oxalate decarboxylase of the white-rot fungus Dichomitus squalens demonstrates a novel enzyme primary structure and non-induced expression on wood and in liquid cultures
Authors: Mäkelä Miia R. , Hildén Kristiina , Hatakka Annele , Lundell Taina K.
Published: July 2009

Oxalate decarboxylase (ODC) catalyses the conversion of oxalic acid to formic acid and CO2in bacteria and fungi. In wood-decaying fungi the enzyme has been linked to the regulation of intra- and extracellular quantities of oxalic acid, which is one of the key components in biological decomposition of wood. ODC enzymes are biotechnologically interesting for their potential in diagnostics, agriculture and environmental applications, e.g. removal of oxalic acid from industrial wastewaters. We identified a novel ODC in mycelial extracts of two wild-type isolates ofDichomitus squalens, and cloned the correspondingDs-odcgene. The primary structure of the Ds-ODC protein contains two conserved Mn-binding cupin motifs, but at the N-terminus, a unique, approximately 60 aa alanine-serine-rich region is found. Real-time quantitative RT-PCR analysis confirmed gene expression when the fungus was cultivated on wood and in liquid medium. However, addition of oxalic acid in liquid cultures caused no increase in transcript amounts, thereby indicating a constitutive rather than inducible expression ofDs-odc. The detected stimulation of ODC activity by oxalic acid is more likely due to enzyme activation than to transcriptional upregulation of theDs-odcgene. Our results support involvement of ODC in primary rather than secondary metabolism in fungi.
Periplasmic nitrate reduction in Wolinella succinogenes: cytoplasmic NapF facilitates NapA maturation and requires the menaquinol dehydrogenase NapH for membrane attachment
Authors: Kern Melanie , Simon Jörg
Published: July 2009

Various nitrate-reducing bacteria produce proteins of the periplasmic nitrate reductase (Nap) system to catalyse electron transport from the membraneous quinol pool to the periplasmic nitrate reductase NapA. The composition of the corresponding nap gene clusters varies but, in addition to napA, genes encoding at least one membrane-bound quinol dehydrogenase module (NapC and/or NapGH) are regularly present. Moreover, some nap loci predict accessory proteins such as the iron–sulfur protein NapF, whose function is poorly understood. Here, the role of NapF in nitrate respiration of the Epsilonproteobacterium Wolinella succinogenes was examined. Immunoblot analysis showed that NapF is located in the membrane fraction in nitrate-grown wild-type cells whereas it was found to be a soluble cytoplasmic protein in a napH deletion mutant. This finding indicates the formation of a membrane-bound NapGHF complex that is likely to catalyse NapH-dependent menaquinol oxidation and electron transport to the iron–sulfur adaptor proteins NapG and NapF, which are located on the periplasmic and cytoplasmic side of the membrane, respectively. The cysteine residues of a CX3CP motif and of the C-terminal tetra-cysteine cluster of NapH were found to be required for interaction with NapF. A napF deletion mutant accumulated the catalytically inactive cytoplasmic NapA precursor, suggesting that electron flow or direct interaction between NapF and NapA facilitated NapA assembly and/or export. On the other hand, NapA maturation and activity was not impaired in the absence of NapH, demonstrating that soluble NapF is functional. Each of the four tetra-cysteine motifs of NapF was modified but only one motif was found to be essential for efficient NapA maturation. It is concluded that the NapGHF complex plays a multifunctional role in menaquinol oxidation, electron transfer to periplasmic NapA and maturation of the cytoplasmic NapA precursor.
Helical Growth of theArabidopsisMutanttortifolia2Does Not Depend on Cell Division Patterns but Involves Handed Twisting of Isolated Cells
Authors: Buschmann Henrik , Hauptmann Monika , Niessing Dierk , Lloyd Clive W. , Schäffner Anton R.
Published: July 2009

Several factors regulate plant organ growth polarity. tortifolia2 (tor2), a right-handed helical growth mutant, has a conservative replacement of Arg-2 with Lys in the α-tubulin 4 protein. Based on a published high-resolution (2.89 Å) tubulin structure, we predict that Arg-2 of α-tubulin forms hydrogen bonds with the GTPase domain of β-tubulin, and structural modeling suggests that these contacts are interrupted in tor2. Consistent with this, we found that microtubule dynamicity is reduced in the tor2 background. We investigated the developmental origin of the helical growth phenotype using tor2. One hypothesis predicts that cell division patterns cause helical organ growth in Arabidopsis thaliana mutants. However, cell division patterns of tor2 root tips appear normal. Experimental uncoupling of cell division and expansion suggests that helical organ growth is based on cell elongation defects only. Another hypothesis is that twisting is due to inequalities in expansion of epidermal and cortical tissues. However, freely growing leaf trichomes of tor2 mutants show right-handed twisting and cortical microtubules form left-handed helices as early as the unbranched stage of trichome development. Trichome twisting is inverted in double mutants with tor3, a left-handed mutant. Single tor2 suspension cells also exhibit handed twisting. Thus, twisting of tor2 mutant organs appears to be a higher-order expression of the helical expansion of individual cells.
Phase I trial of fludarabine, bortezomib and rituximab for relapsed and refractory indolent and mantle cell non‐Hodgkin lymphoma
Authors: Barr Paul M. , Fu Pingfu , Lazarus Hillard M. , Horvath Nancy , Gerson Stanton L. , Koc Omer N. , Bahlis Nizar J. , Snell Michael R. , Dowlati Afshin , Cooper Brenda W.
Published: July 2009

Based on the hypothesis that bortezomib may potentiate fludarabine activity by inhibiting DNA repair, we designed a phase I trial using this combination with rituximab in patients with relapsed and refractory indolent and mantle cell non‐Hodgkin lymphoma. Twenty‐four patients were enrolled. Non‐Hodgkin lymphoma subtypes included 12 patients with follicular lymphoma, four with marginal zone lymphoma, three with lymphoplasmacytic lymphoma, three with mantle cell lymphoma and two with small lymphocytic/chronic lymphocytic leukaemia. Fludarabine and bortezomib were escalated in cohorts of three patients. Rituximab was added to the maximum tolerated dose of fludarabine and bortezomib and added significant dose‐limiting myelosuppression. The maximum tolerated dose was fludarabine 25 mg/m2 on days 1–3, bortezomib 1·3 mg/m2 on days 1, 4, 8, 11, with rituximab 375 mg/m2 on day 1 administered every 21 d. Clinical responses were observed in 11 patients, five of whom were refractory to their most recent treatment regimen. Six additional patients had stable disease for a median of 10 months (range 4–30+). Cumulative myelosuppression and neuropathy was observed. The combination of fludarabine, bortezomib, and rituximab appears to be an active regimen with manageable toxicity for relapsed NHL.
Etanercept as prophylactic psoriatic therapy before interferon-α and ribavirin treatment for active hepatitis C infection
Authors: Behnam S. E. , Hindiyeh R. , Fife D. J. , Jeffes E. W. , Wu J. J.
Published: July 2009

Patients with psoriasis and chronic hepatitis C virus (HCV) infection are a therapeutic challenge. Systemic psoriasis treatment with methotrexate and acitretin can be hepatotoxic, and interferon (IFN)-α for treatment of HCV can worsen psoriasis. Etanercept can be successfully used in patients with psoriasis and HCV. To our knowledge, this is the first case report of etanercept used prophylactically to prevent a psoriatic flare in a patient with HCV treated with IFN-α and ribavirin.
Local and ecoregion effects on fish assemblage structure in tributaries of the Rio Paraíba do Sul, Brazil
Authors: PINTO BENJAMIN CARVALHO TEIXEIRA , ARAUJO FRANCISCO GERSON , RODRIGUES VITOR DANTAS , HUGHES ROBERT M.
Published: July 2009

1. We examined the effects of physical and chemical habitat variables and ecoregions on species occurrence and fish assemblage structure in streams of the Paraíba do Sul basin, in southeast Brazil.

2. Fish and environmental data were collected from 42 sites on 26 first to fourth order streams (1 : 50 000 map scale) in three ecoregions. The sites occurred in one valley and two plateau ecoregions at altitudes of 40–1080 m and distances of 0.1–188 km from the main channel of the Rio Paraíba do Sul. Physical habitat (substratum, riparian cover, habitat types) and water quality (dissolved oxygen, pH, temperature and conductivity) variables were measured at each sampling site.

3. A total of 2684 individuals in 16 families and 59 species were recorded.

4. Ecoregion was a better predictor of the fish assemblage than the other environmental variables, according to the differences between the mean within‐class and mean between‐class similarities in assemblage data.

5. Differing landscape characteristics were associated with differing local variables and thereby with differing fish assemblage structures. Riffles, shrub, grass, dissolved oxygen, conductivity and temperature were closely related to fish assemblage structure.

6. Fish assemblages in sites far from the main river and at higher altitudes also differed from those near the Paraíba do Sul main channel, presumably as a result of differences in connectivity, covarying environmental factors and anthropogenic influence.

7. These results reinforce the importance of understanding how stream communities are influenced by processes and patterns operating at local and regional scales, which will aid water resource managers to target those factors in their management and rehabilitation efforts.
Separation of net ecosystem exchange into assimilation and respiration using a light response curve approach: critical issues and global evaluation
Authors: LASSLOP GITTA , REICHSTEIN MARKUS , PAPALE DARIO , RICHARDSON ANDREW D. , ARNETH ALMUT , BARR ALAN , STOY PAUL , WOHLFAHRT GEORG
Published: July 2009

The measured net ecosystem exchange (NEE) of CO2 between the ecosystem and the atmosphere reflects the balance between gross CO2 assimilation [gross primary production (GPP)] and ecosystem respiration (Reco). For understanding the mechanistic responses of ecosystem processes to environmental change it is important to separate these two flux components. Two approaches are conventionally used: (1) respiration measurements made at night are extrapolated to the daytime or (2) light–response curves are fit to daytime NEE measurements and respiration is estimated from the intercept of the ordinate, which avoids the use of potentially problematic nighttime data. We demonstrate that this approach is subject to biases if the effect of vapor pressure deficit (VPD) modifying the light response is not included. We introduce an algorithm for NEE partitioning that uses a hyperbolic light response curve fit to daytime NEE, modified to account for the temperature sensitivity of respiration and the VPD limitation of photosynthesis. Including the VPD dependency strongly improved the model's ability to reproduce the asymmetric diurnal cycle during periods with high VPD, and enhances the reliability of Reco estimates given that the reduction of GPP by VPD may be otherwise incorrectly attributed to higher Reco. Results from this improved algorithm are compared against estimates based on the conventional nighttime approach. The comparison demonstrates that the uncertainty arising from systematic errors dominates the overall uncertainty of annual sums (median absolute deviation of GPP: 47 g C m−2 yr−1), while errors arising from the random error (median absolute deviation: ∼2 g C m−2 yr−1) are negligible. Despite site‐specific differences between the methods, overall patterns remain robust, adding confidence to statistical studies based on the FLUXNET database. In particular, we show that the strong correlation between GPP and Reco is not spurious but holds true when quasi‐independent, i.e. daytime and nighttime based estimates are compared.
Joint outcomes in patients with haemophilia: the importance of adherence to preventive regimens
Authors: BERNTORP E.
Published: July 2009

Summary.  In patients with severe haemophilia, spontaneous bleeding into joints initiates a sequence of events culminating in disabling arthropathy. Early evidence from Sweden suggested that clotting factor prophylaxis improved patient outcomes. Recent randomized, controlled trials comparing prophylaxis with on‐demand treatment have definitively shown that prophylaxis reduces bleeding and improves joint outcomes in patients with severe haemophilia A. Available evidence also supports the effectiveness of prophylaxis in patients with haemophilia B. In the United States, fewer than half of all patients with severe haemophilia A or B are treated with prophylaxis, and in those receiving such treatment, adherence to prophylactic treatment regimens is low in many age groups. Barriers to prophylaxis include cost, difficulties associated with venous access and the time required for prophylactic infusions. Although concerns around adherence play an important role in the willingness of physicians to prescribe prophylaxis, individualized prophylactic regimens may help increase patient adherence. Clotting factors that are more convenient and less time‐consuming to infuse also may improve adherence to prophylactic therapy. By promoting rigorous adherence to prophylactic clotting factor therapies, physicians may be able to help preserve joint function in patients with severe haemophilia.
Divergent patterns of photosynthetic phosphorus‐use efficiency versus nitrogen‐use efficiency of tree leaves along nutrient‐availability gradients
Authors: Hidaka Amane , Kitayama Kanehiro
Published: July 2009

1.  Nitrogen (N) and phosphorus (P) are essential nutrients for photosynthetic carbon assimilation and most frequently limit primary productivity in terrestrial ecosystems. Efficient use of those nutrients is important for plants growing in nutrient‐poor environments.

2.  We investigated the pattern of photosynthetic phosphorus‐use efficiency (PPUE) in comparison with photosynthetic nitrogen‐use efficiency (PNUE) along gradients of P and N availability across biomes with 340 tree and shrub species. We used both total soil N and P concentration and foliar N/P ratios for indicating nutrient‐availability gradients.

3.  Photosynthetic phosphorus‐use efficiency increased with greater leaf mass per area (LMA) toward decreasing P availability. By contrast, PNUE decreased with greater LMA towards decreasing N and P availability.

4.  The increase in PPUE with decreasing P availability was caused by the net effects of a relatively greater reduction in foliar P concentration and a relatively constant photosynthetic carbon assimilation rate. The decrease in PNUE with decreasing N availability was caused by the effects of a reduction in photosynthetic carbon assimilation rate with greater LMA.

5.

Synthesis. Our results suggest that higher PPUE may be an effective leaf‐level adaptation to P‐poor soils, especially in tropical tree species. Future research should focus on the difference between PPUE and PNUE in relation to leaf economics, physiology and strategy.
Understanding the role of tryptophan and serotonin metabolism in gastrointestinal function
Authors: Keszthelyi D. , Troost F. J. , Masclee A. A. M.
Published: July 2009

Abstract  Tryptophan is the precursor of a wide array of metabolites, which are involved in a variety of aspects of human nutrition and metabolism. Accumulating evidence suggests a role of tryptophan metabolites, especially serotonin (5‐hydroxytryptamin) in intestinal (patho) physiology, although mechanisms of action are still poorly understood. Alterations of serotonin metabolism may give rise to gastrointestinal dysfunction. Recently, it has been postulated that other metabolites of tryptophan, mostly of the kynurenine pathway, also play a role in regulating gut function. This review analyses the current knowledge of the interrelationship between tryptophan metabolic pathways and summarizes the existing scientific evidence regarding the role of tryptophan metabolites in intestinal function and in the pathogenesis of gastrointestinal diseases.
Female Barn Swallows Gain Indirect but not Direct Benefits through Social Mate Choice
Authors: Kojima Wataru , Kitamura Wataru , Kitajima Sachie , Ito Yoko , Ueda Keisuke , Fujita Go , Higuchi Hiroyoshi
Published: July 2009

Female mate choice is responsible for the evolution of male secondary sexual ornaments. If male ornamental traits reflect indirect, genetic benefits and/or direct, material benefits to females, choosy females may benefit from their choice, indirectly and/or directly. We examined a breeding population of Japanese barn swallowsHirundo rustica gutturalisto determine whether male tail streamer length reflected indirect and/or direct benefits to females. There was no significant positive relationship between male streamer length and the number of extra‐pair young (EPY) sired, suggesting that male tail streamers are not a signal of indirect benefits (i.e. good genes theory). In addition, we found no evidence that males with longer streamers fed their offspring more frequently or sired more within‐pair young (WPY). The result indicates that male streamer length probably does not act as a signal of direct benefits. Our finding that the length of tail streamers in Japanese barn swallows plays no role in sexual selection is not consistent with studies on European subspecies, but is consistent with studies on North American subspecies where sexual selection on tail streamer is weak. The present study supports the recent suggestion that the pattern of sexual selection on tail streamer length in barn swallows varies geographically. Instead of tail length, males in better condition sired more EPY and WPY. Males in better condition, however, did not feed their nestling more frequently. These results indicate that females gain indirect benefits but not direct benefits, in terms of feeding of young, on choosing social mates.
Selection and characterization of a novel glyphosate‐tolerant upland cotton (Gossypium hirsutum L.) mutant (R1098)
Authors: Tong X. H. , Daud M. K. , Zhu S. J.
Published: July 2009

With 2 figures and 4 tables

Stepwise selection approach was adopted to obtain glyphosate‐tolerant upland cotton mutant (R1098) from the embryogenic calli of ‘Coker 312’ (Gossypium hirsutum L.). The calli were transferred to the selection medium and multi‐step selection pressure process was carried out until the calli could proliferate in the presence of 20 mm glyphosate. The regenerated plants from the glyphosate‐tolerant calli were analysed for glyphosate response, tolerance of progenies and shikimate accumulation on whole‐plant basis. ‘R1098’ could tolerate 1.48 kg acid equivalent/ha glyphosate. Progeny tests demonstrated that glyphosate tolerance trait was controlled by one dominant gene. Shikimate accumulation assay showed that significantly different amounts of shikimate were present between the mutant (R1098) and its wild parent (Coker 312) after glyphosate treatment. This indicates that ‘R1098’ has sufficient 5‐enolpyruvylshikimate‐3‐phosphate synthase activity in the presence of glyphosate, thereby maintaining normal carbon flow through the shikimate pathway. Moreover, ‘R1098’ offers a greater potential to improve the weed control system in cotton production.
A traceback phenomenon can reveal the origin of prion infection
Authors: Kobayashi Atsushi , Asano Masahiro , Mohri Shirou , Kitamoto Tetsuyuki
Published: July 2009

The transmission of prions to animals with incongruent prion protein (PrP) gene (referred to as cross‐sequence transmission) results in a relatively long incubation period and can generate a new prion strain with unique transmissibility designated as a traceback phenomenon. For example, cross‐sequence transmission of bovine spongiform encephalopathy (BSE) prions to human generated variant Creutzfeldt‐Jakob disease (vCJD) prions which retained the transmissibility to mice expressing bovine PrP. This finding suggests that traceback studies could enable us to identify the origin of prions. There are two distinct phenotypes in dura mater graft‐associated Creutzfeldt‐Jakob disease (dCJD), with the majority represented by a non‐plaque‐type of dCJD (np‐dCJD) and the minority by a plaque‐type of dCJD (p‐dCJD). To identify the origin of p‐dCJD, we performed a traceback study using mice expressing human PrP with methionine homozygosity (129M/M) or valine homozygosity (129V/V) at polymorphic codon 129. The characteristics of p‐dCJD such as the accumulation of abnormal isoform of PrP (PrPSc) intermediate in size between type 1 and type 2, and plaque‐type PrP deposition in the brain were maintained after transmission to the 129M/M mice. Furthermore, the 129V/V mice were more susceptible to p‐dCJD prions than the 129M/M mice and produced type 2 PrPSc that were identical in size to those from the 129V/V mice inoculated with sporadic CJD prions from a patient with 129V/V and type 2 PrPSc (sCJD‐VV2). In addition, we performed intracerebral transmission of sCJD‐VV2 prions to the 129M/M mice as an experimental model for p‐dCJD. These 129M/M mice showed the accumulation of the intermediate type PrPSc and plaque‐type PrP deposition in the brain. These results suggest that p‐dCJD could be caused by cross‐sequence transmission of sCJD‐VV2 prions to individuals with the 129M/M genotype.
Dura mater graft‐associated Creutzfeldt‐Jakob disease in Japan: Clinicopathological and molecular characterization of the two distinct subtypes
Authors: Yamada Masahito , Noguchi‐Shinohara Moeko , Hamaguchi Tsuyoshi , Nozaki Ichiro , Kitamoto Tetsuyuki , Sato Takeshi , Nakamura Yosikazu , Mizusawa Hidehiro
Published: July 2009

Up to February 2008, a total of 132 patients with dura mater graft‐associated Creutzfeldt‐Jakob disease (dCJD) have been identified in Japan, accounting for a majority of the world's patients with dCJD. The patients received dura mater grafts from 1978 to 1993. Lyodura® (B. Braun, Melsungen, Germany) was used for all the patients in whom the brand name of the dura mater could be identified. After the incubation period of 1 to 25 years (mean, 11.8 years), CJD appeared from 1985 through to 2006. We analyzed clinical, pathological, and molecular features in 74 patients with dCJD who had been prospectively registered by the CJD Surveillance Committee. The cases of dCJD could be classified into two distinct clinicopathological phenotypes: a non‐plaque type, showing typical features identical with those of classic CJD, and a plaque type, characterized by atypical features, including slow progression, lack of or late occurrence of periodic sharp wave complexes on EEG, and plaque formation in the brain. The plaque type accounted for one‐third of the pathologically confirmed or clinically diagnosed cases of dCJD. The non‐plaque type was associated with methionine homozygosity at codon 129 (129M/M) of the PrP gene in all patients, except for in one patient with the 129M/valine (V) genotype and type 1 protease‐resistant PrP (PrPres), whereas the plaque type was always associated with the 129M/M genotype and the intermediate type between types 1 and 2 of PrPres in all cases. Thus, the clinicopathological and molecular features of the plaque type are distinct from those of the non‐plaque type, suggesting contamination of the dura mater grafts with different prion strains.
Pulmonary sclerosing haemangioma mimicking lung cancer on PET scan
Authors: HSU Po‐Kuei , CHENG Hsu‐Fong , YEH Yi‐Chen , WU Yu‐Chung , HSU Wen‐Hu
Published: July 2009

Sclerosing haemangioma is an uncommon lung tumour that typically presents as a solitary, peripheral pulmonary nodule in the lower lobe. Little is known of the appearance of these tumours on FDG‐PET scan. We report two patients with sclerosing haemangioma with increased uptake on FDG‐PET scan, which complicated the preoperative work‐up. Although the CT scan features of these two masses were compatible with the differential diagnosis of sclerosing haemangioma, the central location and increased uptake on FDG‐PET scan raised the suspicion of malignancy. We conclude that centrally located large sclerosing haemangiomas may be avid on FDG‐PET scan, and that familiarity with this false positive finding helps in the diagnosis of a solitary pulmonary nodule.
Rounded atelectasis and respiratory compromise secondary to pergolide use
Authors: BLOOM Chloe I. , WILSON Graeme E.
Published: July 2009

Rounded atelectasis is an unusual form of peripheral atelectasis that develops as a consequence of pleural disease. It is usually thought to be a benign process after malignancy and infection have been excluded. Pergolide is an ergot‐derived dopamine agonist that has been associated with pleuropulmonary fibrosis and fibrotic cardiac valve disease. Pergolide‐associated rounded atelectasis has occurred in patients with known asbestos exposure. We report a patient with no known asbestos exposure who developed rounded atelectasis and subsequent symptomatic diffuse restrictive pleural disease. Physicians should consider drugs early on in their work‐up of rounded atelectasis as discontinuation of the agent may reverse the process.
Endogenous BDNF is required for myelination and regeneration of injured sciatic nerve in rodents
Authors: Zhang Jian‐Yi , Luo Xue‐Gang , Xian Cory J. , Liu Zhong‐Hao , Zhou Xin‐Fu
Published: July 2009

Following a peripheral nerve injury, brain‐derived neurotrophic factor (BDNF) and the p75 neurotrophin receptor are upregulated in Schwann cells of the Wallerian degenerating nerves. However, it is not known whether the endogenous BDNF is critical for the functions of Schwann cells and regeneration of injured nerve. Treatment with BDNF antibody was shown to retard the length of the regenerated nerve from injury site by 24%. Histological and ultrastructural examination showed that the number and density of myelinated axons in the distal side of the lesion in the antibody‐treated mice was reduced by 83%. In the BDNF antibody‐treated animals, there were only distorted and disorganized myelinated fibres in the injured nerve where abnormal Schwann cells and phagocytes were present. As a result of nerve degeneration in BDNF antibody‐treated animals, subcellular organelles, such as mitochondria, disappeared or were disorganized and the laminal layers of the myelin sheath were loosened, separated or collapsed. Our in situ hybridization revealed that BDNF mRNA was expressed in Schwann cells in the distal segment of lesioned nerve and in the denervated muscle fibres. These results indicate that Schwann cells and muscle fibres may contribute to the sources of BDNF during regeneration and that the deprivation of endogenous BDNF results in an impairment in regeneration and myelination of regenerating axons. It is concluded that endogenous BDNF is required for peripheral nerve regeneration and remyelination after injury.
Fear conditioning in C57/BL/6 and DBA/2 mice: variability in nucleus accumbens function according to the strain predisposition to show contextual‐ or cue‐based responding
Authors: Ammassari‐Teule Martine , Passino Enrica , Restivo Leonardo , De Marsanich Benedetta
Published: July 2009

The contribution of the nucleus accumbens shell, the dorsal hippocampus, and the basolateral amygdala to contextual and explicit cue fear conditioning was assessed in C57BL/6 (C57) and DBA/2 (DBA) mice showing differences in processing contextual information associated with consistent but non‐pathological variations in hippocampal functionality. Mice from both strains with bilateral ibotenic acid or sham lesions located in each area were introduced in a conditioning chamber and exposed twice to the pairing of a tone (2 × 8 s, 2000 Hz, 80 dB) with a shock (2 s, 0.7 mA). On the following day, mice were first exposed to the training context then to the tone in a different context. Freezing behaviour was scored in all situations. C57 showed more freezing to the context than to the tone whereas DBA showed more freezing to the tone than to the context. In C57, both nucleus accumbens and hippocampal lesions impaired acquisition of contextual fear conditioning but paradoxically improved acquisition of cue fear conditioning, whereas amygdala lesions disrupted performance in every task. In DBA, nucleus accumbens lesions, like amygdala lesions, impaired acquisition of both contextual and cue fear conditioning, whereas hippocampal lesions did not produce any effect. The parallelism between the effect of nucleus accumbens and hippocampus lesions in C57, and between the effect of nucleus accumbens and amygdala lesions in DBA points to a variability in nucleus accumbens function according to the strain specialization to develop context‐ or cue‐based responding.
Role of interleukin‐1β and tumour necrosis factor‐α in lipopolysaccharide‐induced sickness behaviour: a study with interleukin‐1 type I receptor‐deficient mice
Authors: Bluthé Rose‐Marie , Layé Sophie , Michaud Bruno , Combe Chantal , Dantzer Robert , Parnet Patricia
Published: July 2009

Interleukin‐1 (IL‐1) mediates symptoms of sickness during the host response to infection. IL‐1 exerts its effects via several subtypes of receptors. To assess the role of IL‐1 receptor type I (IL‐1RI) in the sickness‐inducing effects of IL‐1, IL‐1β and the cytokine inducer lipopolysaccharide were administered to IL‐1RI‐deficient mice (IL‐1RI–/–). Sickness was assessed by depression of social exploration, anorexia, immobility and body weight loss. IL‐1RI–/– mice were resistant to the sickness‐inducing effects of IL‐1β administered intraperitoneally (2 µg/mouse) and intracerebroventricularly (2 ng/mouse), but still fully responsive to lipopolysaccharide administered intraperitoneally (2.5 µg/mouse) and intracerebroventricularly (3 ng/mouse). The sensitivity of IL‐1RI–/– mice to lipopolysaccharide was not due to a higher brain expression of proinflammatory cytokines other than IL‐1, since lipopolysaccharide‐induced expression of brain IL‐1 β, tumour necrosis factor‐α (TNF‐α) and IL‐6 transcripts were identical in IL‐1RI–/– and control mice when measured by semiquantitative reverse‐transcriptase polymerase chain reaction 1 h after treatment. Blockade of TNF‐α action in the brain by intracerebroventricular administration of a fragment of the soluble TNF receptor, TNF binding protein (3.6 µg/mouse), attenuated the depressive effects of intraperitoneal injection of lipopolysaccharide (1 µg/mouse) on behaviour in IL‐1RI–/– but not in control mice. Since IL‐1RI–/– mice were not more sensitive to intracerebroventricularly TNF‐α (50 ng) than control mice, these results indicate that IL‐1RI mediates the sickness effect of IL‐1 and that TNF‐α simply replaces IL‐1 when this last cytokine is deficient.
Differential calbindin‐immunoreactivity in dopamine neurons projecting to the rat striatal complex
Authors: Barrot Michel , Calza Laura , Pozza Monica , Le Moal Michel , Piazza Pier Vincenzo
Published: July 2009

The calcium‐binding protein calbindin‐D28K is an anatomical marker that has been associated with resistance to neurodegeneration and with the electrophysiological characteristics of neurons. In this study, we compared the presence of calbindin in dopamine neurons projecting to three distinct functional regions of the striatal complex: the striatum, and the core and the shell of the nucleus accumbens. After iontophoretic injections of Fluoro‐Gold in the dopaminergic terminal fields, the presence of tyrosine hydroxylase and calbindin were immunohistochemically assessed in the mesencephalon. It was found that the proportion of cells expressing calbindin was highest in the dopamine cells projecting to the core (72%), intermediate in the cells projecting to the shell (51%) and lowest in the cells projecting to the dorsolateral striatum (2.6%). These results do not support the idea that calbindin is a sufficient condition to confer resistance to neurodegeneration because shell‐projecting neurons seem the most resistant to it. The present data also raise the question of the role of calbindin in the differences in firing characteristics among dopamine neurons projecting to the striatal complex.
Saccharin activates cation conductance via inositol 1,4,5‐trisphosphate production in a subset of isolated rod taste cells in the frog
Authors: Okada Yukio , Fujiyama Rie , Miyamoto Takenori , Sato Toshihide
Published: July 2009

The transduction mechanism of the conductance activated by saccharin was analysed in isolated bullfrog taste cells under whole‐cell voltage‐clamp. Bath application of 30 mm saccharin induced an inward current of −34 ± 12 pA (mean ± SEM, n = 10) at a membrane potential of −50 mV in 10 (23%) of 44 rod cells. The concentration–response relationship for the saccharin‐gated current was consistent with that of the gustatory neural response. The saccharin‐induced current was accompanied with a conductance increase under internal low Cl– condition (ECl = −56 mV), suggesting that saccharin activated a cation conductance. The reversal potential of the saccharin‐induced current was −17 ± 2 mV (n = 10). Intracellular dialysis of 0.5 mm guanosine 5′‐O‐(2‐thiodiphosphate) (GDP‐β‐S) completely blocked the saccharin‐induced response, suggesting the involvement of a G protein in the transduction. The dialysis of heparin (1 mg/mL) also inhibited the response almost completely, but the dialysis of 1 mm 8‐Br‐cAMP did not affect the response significantly. Intracellular 50 µm inositol 1,4,5‐trisphosphate (1,4,5 InsP3) also induced the inward current in five (38%) of 13 rod cells, but intracellular Pasteurella multocida toxin (5 µg/mL, Gαq‐coupled PLC activator) did not elicit any response in the cells. The results suggest that saccharin mainly activates a cation conductance in frog taste cells through the mediation of IP3 production.
GOING FROM PRINCIPLES TO RULES IN RESEARCH ETHICS
Authors: SACHS BENJAMIN
Published: July 2009

In research ethics there is a canon regarding what ethical rules ought to be followed by investigators vis‐à‐vis their treatment of subjects and a canon regarding what fundamental ethical principles apply to the endeavor. What I aim to demonstrate here is that several of the rules find no support in the principles. This leaves anyone who would insist that we not abandon those rules in the difficult position of needing to establish that we are nevertheless justified in believing in the validity of the rules. I conclude by arguing that this is not likely to be accomplished.

The rules I call into question are the rules requiring:

that studies be designed in a scientifically valid way

that risks to subjects be minimized

that subjects be afforded post‐trial access to experimental interventions

that inducements paid to subjects not be counted as a benefit to them

that inducements paid to subjects not be ‘undue’

that subjects must remain free to withdraw from the study at any time for any reason without penalty

Both canons, the canon on principles and the canon on rules, are found in the overlap among ethical pronouncements that are themselves canonical: the Nuremberg Code, the Declaration of Helsinki, the Belmont Report, CIOMS's International Ethical Guidelines for Biomedical Research Involving Human Subjects, and NBAC's 2001 report, Ethical Issues in International Research: Clinical Trials in Developing Countries.