bluuebunny/crossref_metadata_2025 huggingface dataset:
Intra- and intermolecular domain interactions among novel two-component system proteins coded by Rv0600c, Rv0601c and Rv0602c of Mycobacterium tuberculosis
Authors: Shrivastava Rashmi , Ghosh Ananta Kumar , Das Amit Kumar
Published: February 2009

Two-component signal transduction pathways comprising a histidine kinase and its cognate response regulator play a dominant role in the adaptation of Mycobacterium tuberculosis to its host, and its virulence, pathogenicity and latency. Autophosphorylation occurs at a conserved histidine of the histidine kinase and subsequently the phosphoryl group is transferred to the conserved aspartate of its cognate response regulator. Among the twelve two-component systems of M. tuberculosis, Rv0600c (HK1), Rv0601c (HK2) and Rv0602c (TcrA) are annotated as a unique three-protein two-component system. HK1 contains an ATP-binding domain, and HK2, a novel Hpt mono-domain protein, contains the conserved phosphorylable histidine residue. HK1 and HK2 complement each other's functions. Interactions among different domains of the HK1, HK2 and TcrA proteins were studied using a yeast two-hybrid system. Self-interaction was observed for HK2 but not for HK1 or TcrA. HK2 was found to interact reasonably well with both HK1 and TcrA, but HK1 interacted weakly with TcrA. The conserved aspartate-containing receiver domain of TcrA interacted well with HK2 but not with HK1. These results suggest the existence of a novel signalling mechanism amongst HK1–HK2–TcrA, and a model for this mechanism is proposed.
Is gas-discharge plasma a new solution to the old problem of biofilm inactivation?
Authors: Joaquin Jonathan C. , Kwan Calvin , Abramzon Nina , Vandervoort Kurt , Brelles-Mariño Graciela
Published: February 2009

Conventional disinfection and sterilization methods are often ineffective with biofilms, which are ubiquitous, hard-to-destroy microbial communities embedded in a matrix mostly composed of exopolysaccharides. The use of gas-discharge plasmas represents an alternative method, since plasmas contain a mixture of charged particles, chemically reactive species and UV radiation, whose decontamination potential for free-living, planktonic micro-organisms is well established. In this study, biofilms were produced using Chromobacterium violaceum, a Gram-negative bacterium present in soil and water and used in this study as a model organism. Biofilms were subjected to an atmospheric pressure plasma jet for different exposure times. Our results show that 99.6 % of culturable cells are inactivated after a 5 min treatment. The survivor curve shows double-slope kinetics with a rapid initial decline in c.f.u. ml−1 followed by a much slower decline with D values that are longer than those for the inactivation of planktonic organisms, suggesting a more complex inactivation mechanism for biofilms. DNA and ATP determinations together with atomic force microscopy and fluorescence microscopy show that non-culturable cells are still alive after short plasma exposure times. These results indicate the potential of plasma for biofilm inactivation and suggest that cells go through a sequential set of physiological and morphological changes before inactivation.
Identification of non-flagellar genes involved in swarm cell differentiation using a Bacillus thuringiensis mini-Tn10 mutant library
Authors: Salvetti Sara , Celandroni Francesco , Ceragioli Mara , Senesi Sonia , Ghelardi Emilia
Published: February 2009

Swarming is a social phenomenon that enables motile bacteria to move co-ordinately over solid surfaces. The molecular basis regulating this process is not completely known and may vary among species. Insertional mutagenesis of a swarming-proficientBacillus thuringiensisstrain was performed, by use of the transposon mini-Tn10, to identify novel genetic determinants of swarming that are dispensable for flagellation, swimming motility, chemotaxis and active growth. Among the 67 non-swarming mutants obtained, six were selected that showed no defect in flagellar assembly and function, chemotaxis or growth rate. Sequence analysis of DNA flanking the transposon insertion led to the identification of previously uncharacterized genes that are involved in the development of swarming colonies byB. thuringiensisand that are highly conserved in all members of theBacillus cereus sensu latogroup. These genes encode non-flagellar proteins with putative activity as sarcosine oxidase, catalase-2, amino acid permease, ATP-binding cassette transporter, dGTP triphosphohydrolase and acetyltransferase. Functional analysis of two of the isolated mutants demonstrated that swarming differentiation depends on the intracellular levels of the osmoprotectant glycine betaine and on the quantity of synthesized phenazine secondary metabolites. The finding that proteins involved in diverse physiological processes have a role in swarming motility underlines the complexity of the molecular mechanisms governing this behaviour inB. thuringiensis.
Identification of neisserial DNA binding components
Authors: Lång Emma , Haugen Kristine , Fleckenstein Burkhard , Homberset Håvard , Frye Stephan A. , Ambur Ole Herman , Tønjum Tone
Published: February 2009

Neisseria meningitidis, a causative agent of meningitis and septicaemia, expresses type IV pili, a feature correlating with the uptake of exogenous DNA from the environment by natural transformation. The outer membrane complex PilQ, through which pili are extruded and retracted, has previously been shown to bind DNA in its pore region. In order to further elucidate how DNA is transported across the membranes, we searched for DNA binding proteins within the meningococcal inner membrane. Inner membrane fractions from a panel of neisserial strains were subjected to a solid-phase overlay assay with DNA substrates, and MS was subsequently employed to identify proteins that bind DNA. A number of DNA binding components were detected, including the pilus biogenesis component PilG, the competence protein ComL, and the cell division ATP-binding protein FtsE, as well as two hypothetical proteins. The DNA binding activity of these components was not dependent on the presence of the neisserial DNA uptake sequence. Null mutants, corresponding to each of the proteins identified, were constructed to assess their phenotypes. Only mutants defective in pilus biogenesis were non-competent and non-piliated. The DNA binding activity of the pilus biogenesis components PilQ and PilG and the phenotypes of their respective null mutants suggest that these proteins are directly involved as players in natural transformation, and not only indirectly, through pilus biogenesis.
A type II secreted RNase of Legionella pneumophila facilitates optimal intracellular infection of Hartmannella vermiformis
Authors: Rossier Ombeline , Dao Jenny , Cianciotto Nicholas P.
Published: February 2009

Type II protein secretion plays a role in a wide variety of functions that are important for the ecology and pathogenesis of Legionella pneumophila. Perhaps most dramatic is the critical role that this secretion pathway has in L. pneumophila intracellular infection of aquatic protozoa. Recently, we showed that virulent L. pneumophila strain 130b secretes RNase activity through its type II secretion system. We now report the cloning and mutational analysis of the gene (srnA) encoding that novel type of secreted activity. The SrnA protein was defined as being a member of the T2 family of secreted RNases. Supernatants from mutants inactivated for srnA completely lacked RNase activity, indicating that SrnA is the major secreted RNase of L. pneumophila. Although srnA mutants grew normally in bacteriological media and human U937 cell macrophages, they were impaired in their ability to grow within Hartmannella vermiformis amoebae. This finding represents the second identification of a L. pneumophila type II effector being necessary for optimal intracellular infection of amoebae, with the first being the ProA zinc metalloprotease. Newly constructed srnA proA double mutants displayed an even larger infection defect that appeared to be the additive result of losing both SrnA and ProA. Overall, these data represent the first demonstration of a secreted RNase promoting an intracellular infection event, and support our long-standing hypothesis that the infection defects of L. pneumophila type II secretion mutants are due to the loss of multiple secreted effectors.
Mechanism of downregulation of photosystem I content under high-light conditions in the cyanobacterium Synechocystis sp. PCC 6803
Authors: Muramatsu Masayuki , Sonoike Kintake , Hihara Yukako
Published: February 2009

Downregulation of photosystem I (PSI) content is an essential process for cyanobacteria to grow under high-light (HL) conditions. In apmgA(sll1968) mutant ofSynechocystissp. PCC 6803, the levels of PSI content, chlorophyll and transcripts of thepsaABgenes encoding reaction-centre subunits of PSI could not be maintained low during HL incubation, although the causal relationship among these phenotypes remains unknown. In this study, we modulated the activity ofpsaABtranscription or that of chlorophyll synthesis to estimate their contribution to the regulation of PSI content under HL conditions. Analysis of thepsaAB-OX strain, in which thepsaABgenes were overexpressed under HL conditions, revealed that the amount ofpsaABtranscript could not affect PSI content by itself. Suppression of chlorophyll synthesis by an inhibitor, laevulinic acid, in thepmgAmutant revealed that chlorophyll availability could be a determinant of PSI content under HL. It was also suggested that chlorophyll content under HL conditions is mainly regulated at the level of 5-aminolaevulinic acid synthesis. We conclude that, upon the shift to HL conditions, activities ofpsaABtranscription and of 5-aminolaevulinic acid synthesis are strictly downregulated by regulatory mechanism(s) independent of PmgA during the first 6 h, and then a PmgA-mediated regulatory mechanism becomes active after 6 h onward of HL incubation to maintain these activities at a low level.
Characterization of sulphonamide-resistant Escherichia coli using comparison of sul2 gene sequences and multilocus sequence typing
Authors: Trobos Margarita , Christensen Henrik , Sunde Marianne , Nordentoft Steen , Agersø Yvonne , Simonsen Gunnar S. , Hammerum Anette M. , Olsen John E.
Published: February 2009

The sul2 gene encodes sulphonamide resistance (SulR) and is commonly found in Escherichia coli from different hosts. We typed E. coli isolates by multilocus sequence typing (MLST) and compared the results to sequence variation of sul2, in order to investigate the relation to host origin of pathogenic and commensal E. coli strains and to investigate whether transfer of sul2 into different genomic lineages has happened multiple times. Sixty-eight E. coli isolated in Denmark and Norway from different hosts and years were MLST typed and sul2 PCR products were sequenced and compared. PFGE was performed in a subset of isolates. All isolates were divided into 45 different sequence types (STs), with clonal complexes CC10, CC23, CC168, CC350 and CC69 being the most frequent. The sul2 gene from the majority of E. coli strains had only two point mutations, at positions 159 and 197, leading to a synonymous and a non-synonymous change, respectively. Five strains had extra single mutations. All poultry, poultry meat, and Danish human blood isolates had the same sul2 ST and some of these strains clustered under the same MLST STs, indicating that they shared habitats. Most PFGE profiles clustered according to source, but some included different sources. SulR
E. coli from different animals, food, human faeces and infections did not cluster according to their origin, suggesting that these habitats share E. coli and sul2 gene types. However, while pig isolates on one occasion clustered with urinary tract infection isolates, poultry isolates seemed more related to isolates from bloodstream infections in humans. Presence of mainly two types of the sul2 gene in both human and animal isolates, irrespective of date and geography, and the presence of both types in the same clonal lineages, suggest horizontal transfer of sul2.
The cell-envelope proteome of Bifidobacterium longum in an in vitro bile environment
Authors: Ruiz Lorena , Couté Yohann , Sánchez Borja , de los Reyes-Gavilán Clara G. , Sanchez Jean-Charles , Margolles Abelardo
Published: February 2009

Host–bacteria interactions are often mediated via surface-associated proteins. The identification of these proteins is an important goal of bacterial proteomics. To address how bile can influence the cell-envelope proteome of Bifidobacterium longum biotype longum NCIMB 8809, we analysed its membrane protein fraction using stable isotope labelling of amino acids in cell culture (SILAC). We were able to identify 141 proteins in the membrane fraction, including a large percentage of the theoretical transporters of this species. Moreover, the envelope-associated soluble fraction was analysed using different subfractionation techniques and differential in-gel fluorescence electrophoresis (DIGE). This approach identified 128 different proteins. Some of them were well-known cell wall proteins, but others were highly conserved cytoplasmic proteins probably displaying a ‘moonlighting’ function. We were able to identify 11 proteins in the membrane fraction and 6 proteins in the envelope-associated soluble fraction whose concentration varied in the presence of bile. Bile promoted changes in the levels of proteins with important biological functions, such as some ribosomal proteins and enolase. Also, oligopeptide-binding proteins were accumulated on the cell surface, which was reflected in a different tripeptide transport rate in the cells grown with bile. The data reported here will provide the first cell-envelope proteome map for B. longum, and may contribute to understanding the bile tolerance of these bacteria.
Biofilms and type III secretion are not mutually exclusive in Pseudomonas aeruginosa
Authors: Mikkelsen H. , Bond N. J. , Skindersoe M. E. , Givskov M. , Lilley K. S. , Welch M.
Published: February 2009

Pseudomonas aeruginosais a Gram-negative opportunistic pathogen that causes acute and chronic infections in immunocompromised individuals. It is also a model organism for bacterial biofilm formation. Acute infections are often associated with planktonic or free-floating cells, high virulence and fast growth. Conversely, chronic infections are often associated with the biofilm mode of growth, low virulence and slow growth that resembles that of planktonic cells in stationary phase. Biofilm formation and type III secretion have been shown to be reciprocally regulated, and it has been suggested that factors related to acute infection may be incompatible with biofilm formation. In a previous proteomic study of the interrelationships between planktonic cells, colonies and continuously grown biofilms, we showed that biofilms under the growth conditions applied are more similar to planktonic cells in exponential phase than to those in stationary phase. In the current study, we investigated how these conditions influence the production of virulence factors using a transcriptomic approach. Our results show that biofilms express the type III secretion system, whereas planktonic cells do not. This was confirmed by the detection of PcrV in the cellular and secreted fractions of biofilms, but not in those of planktonic cells. We also detected the type III effector proteins ExoS and ExoT in the biofilm effluent, but not in the supernatants of planktonic cells. Biofilm formation and type III secretion are therefore not mutually exclusive inP. aeruginosa, and biofilms could play a more active role in virulence than previously thought.
Structural and thermal properties of the monoclinic Lu2SiO5single crystal: evaluation as a new laser matrix
Authors: Cong Hengjiang , Zhang Huaijin , Wang Jiyang , Yu Wentao , Fan Jiandong , Cheng Xiufeng , Sun Shangqian , Zhang Jian , Lu Qingming , Jiang Chunjian , Boughton Robert I.
Published: February 2009

The crystal structure of monoclinic Lu2SiO5(LSO) crystals, grown by the Czochralski method, was determined at room temperature by X-ray diffraction. The unit-cell parameters area= 10.2550 (2),b= 6.6465 (2),c= 12.3626 (4) Å, β = 102.422 (1)° in space groupI2/a. The linear thermal expansion tensor was determined along thea,b,candc* directions over the temperature range from 303.15 to 768.15 K, and the principal coefficients of the thermal expansion tensor are found to be αI= −1.0235 × 10−6 K, αII= 4.9119 × 10−6 K and αIII= 10.1105 × 10−6 K. The temperature dependence of the cell volume and monoclinic angle were also evaluated. In addition, the specific heat and the thermal diffusivity were measured over the temperature ranges from 293.15 to 673.15 K and from 303.15 to 572.45 K, respectively. As a result, the anisotropic thermal conductivity could be calculated and is reported for the first time, to the best of the authors' knowledge. The specific heat capacity of LSO is 139.54 J mol−1 K−1, and the principal components of the thermal conductivity arekI= 2.26 W m−1 K−1,kII= 3.14 W m−1 K−1andkII= 3.67 W m−1 K−1at 303.15 K. A new structure model was proposed to better understand the relationships between the crystal structure and anisotropic thermal properties. In comparison with other laser matrix crystals, it is found that LSO possesses relatively large anisotropic thermal properties, and owing to its small heat capacity it has a moderate thermal conductivity, which is similar to those of the tungstates but lower than those of the vanadates.
Two-dimensional hydrogen-bonded networks in 1-(diaminomethylene)thiouron-1-ium nitrate and bis[1-(diaminomethylene)thiouron-1-ium] phosphonate monohydrate
Authors: Janczak Jan , Perpétuo Genivaldo Julio
Published: February 2009

Crystals of the title compounds, C2H7N4S+·NO3−, (I), and 2C2H7N4S+·HPO32−·H2O, (II), are built up from 1-(diaminomethylene)thiouron-1-ium cations and nitrate anions in (I), and from phosphonate anions and water molecules in (II). In both crystals, the cations and anions are linked togetherviaN—H...O hydrogen bonds. The 1-(diaminomethylene)thiouron-1-ium cations exhibit a twisted conformation. Both arms of the cations are planar and are turned in opposite directions around the C—N bond involving the central N atom. Hydrogen-bonding interactions join oppositely charged units into layers in the nitrate salt and into double layers in the phosphonate monohydrate salt. In addition, the structures are stabilized by π–π interactions between the delocalized π bonds of the cations. The significance of this study lies in the illustration of the differences between the supramolecular aggregations in the nitrate and phosphonate salts of a small organic molecule. The different geometries of the counter-ions and their different potential for hydrogen-bond formation results in markedly different hydrogen-bond arrangements.
Development of taxon‐specific sequence characterized amplified region (SCAR) markers based on actin sequences and DNA amplification fingerprinting (DAF): a case study in the Phoma exigua species complex
Authors: AVESKAMP MAIKEL M. , WOUDENBERG JOYCE H.C. , DE GRUYTER JOHANNES , TURCO ELENA , GROENEWALD JOHANNES Z. , CROUS PEDRO W.
Published: February 2009

Phoma exigua is considered to be an assemblage of at least nine varieties that are mainly distinguished on the basis of host specificity and pathogenicity. However, these varieties are also reported to be weak pathogens and secondary invaders on non‐host tissue. In practice, it is difficult to distinguish P. exigua from its close relatives and to correctly identify isolates up to the variety level, because of their low genetic variation and high morphological similarity. Because of quarantine issues and phytosanitary measures, a robust DNA‐based tool is required for accurate and rapid identification of the separate taxa in this species complex. The present study therefore aims to develop such a tool based on unique nucleotide sequence identifiers. More than 60 strains of P. exigua and related species were compared in terms of partial actin gene sequences, or analysed using DNA amplification fingerprinting (DAF) with short, arbitrary, mini‐hairpin primers. Fragments in the fingerprint unique to a single taxon were identified, purified and sequenced. Alignment of the sequence data and subsequent primer trials led to the identification of taxon‐specific sequence characterized amplified regions (SCARs), and to a set of specific oligonucleotide combinations that can be used to identify these organisms in plant quarantine inspections.
Relationships between morphological and sedimentological parameters in source‐to‐sink systems: a basis for predicting semi‐quantitative characteristics in subsurface systems
Authors: Sømme Tor O. , Helland‐Hansen William , Martinsen Ole J. , Thurmond John B.
Published: February 2009

The study of source‐to‐sink systems relates long‐term variations in sediment flux to morphogenic evolution of erosional–depositional systems. These variations are caused by an intricate combination of autogenic and allogenic forcing mechanisms that operate on multiple time scales – from individual transport events to large‐scale filling of basins. In order to achieve a better understanding of how these mechanisms influence morphological characteristics on different scales, 29 submodern source‐to‐sink systems have been investigated. The study is based on measurements of morphological parameters from catchments, shelves and slopes derived from a ∼1 km global digital elevation model dataset, in combination with data on basin floor fans, sediment supply, water discharge and deposition rates derived from published literature. By comparing various morphological and sedimentological parameters within and between individual systems, a number of relationships governing system evolution and behaviour are identified. The results suggest that the amount of low‐gradient floodplain area and river channel gradient are good indicators for catchment storage potential. Catchment area and river channel length is also related to shelf area and shelf width, respectively. Similarly to the floodplain area, these parameters are important for long‐term storage of sediment on the shelf platform. Additionally, the basin floor fan area is correlative to the long‐term deposition rate and the slope length. The slope length thus proves to be a useful parameter linking proximal and distal segments in source‐to‐sink systems. The relationships observed in this study provide insight into segment scale development of source‐to‐sink systems, and an understanding of these relationships in modern systems may result in improved knowledge on internal and external development of source‐to‐sink systems over geological time scales. They also allow for the development of a set of semi‐quantitative guidelines that can be used to predict similar relationships in other systems where data from individual system segments are missing or lacking.
Depositional architecture of a low‐gradient ramp shelf in an epicontinental sea: the lower Cretaceous of Svalbard
Authors: Midtkandal I. , Nystuen J. P.
Published: February 2009

Facies belts have been recorded using conventional field methods in the Lower Cretaceous Helvetiafjellet Formation in Spitsbergen, Svalbard. The formation was deposited upon a regional subaerial unconformity (SU) that developed downdip from an incised valley complex to the W, NW and possibly north of Spitsbergen during fall in relative sea level and incision into the marine Rurikfjellet Formation. The unconformity likely resulted from crustal tectonics related to the formation of the proto‐Amerasian basin. The unconformity was initially covered by braided stream facies sand and locally by small bay head delta deposits. Further rise in relative sea level resulted in transgression, and the initial braidplain turned into a low‐sloping shelf ramp of coastal plain and paralic to marine environments. Balance between increase in accommodation space and rate of sediment supply gave rise to aggradational stacking architecture of the middle and upper part of the Helvetiafjellet Formation, until further rise in sea level turned the shelf again into an open marine setting with deposition of the overlying Carolinefjellet Formation. Architectural pattern of fluvial distributary channel sandstone bodies in the aggradational succession is explained within the framework of the Boreal basin, not only the Spitsbergen outcrop domain as in previous models. The revised depositional model for the Helvetiafjellet Formation implies that fluvial systems in similar emerged epicontinental basins may have large potential to carry sand several hundreds of kilometres out into the basin with formation of fluvial sandstone intervals of large regional extent, bounded by semi‐parallel stratigraphic surfaces transecting time‐lines at very low angles. Sandstone bodies with clinoform geometry are in this setting restricted to local small‐scale paralic deltas and shoreface deposits.
Lack of pharmacokinetic bioequivalence between generic and branded amoxicillin formulations. A post‐marketing clinical study on healthy volunteers
Authors: Del Tacca Mario , Pasqualetti Giuseppe , Di Paolo Antonello , Virdis Agostino , Massimetti Gabriele , Gori Giovanni , Versari Daniele , Taddei Stefano , Blandizzi Corrado
Published: February 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Generic medicinal products are ‘copies’ of patented drugs and can be marketed at low cost following patent expiration of the brand‐name preparations.

• Although the development of generic medicinal products is regulated by specific guidelines, a number of issues and concerns continue to undermine the confidence of physicians and patients in generic drugs.

WHAT THIS STUDY ADDS

• The present findings open interesting perspectives for the discussion of the quality of generic drugs in the postmarketing setting.

• In particular, our trial shows that postmarketing evaluation of bioequivalence between branded amoxicillin and its generic copies might result in lack of interchangeability.

AIMS

There are concerns about the quality of generic drugs in the postmarketing setting. The aim was to establish whether two generic formulations of amoxicillin, available on the Italian market, fulfil the criteria for clinical pharmacokinetic bioequivalence vs. the branded drug.

METHODS

Two generic amoxicillin products (generic A and B) were selected among four fast‐release tablet formulations available on the Italian market. Twenty‐four healthy adult volunteers of either sex participated to a single‐dose, randomized, three‐treatment, crossover, single‐blind bioequivalence study designed to compare generic A and B with branded amoxicillin. Plasma samples were collected at preset times for 24 h after dosing, and assayed for amoxicillin levels by high‐performance liquid chromatography.

RESULTS

Ninety percent confidence intervals of AUC ratios were 0.8238, 1.0502 (ratio 0.9302) and 0.8116, 1.1007 (ratio 0.9452) for generic A and B vs. branded amoxicillin, respectively. Ninety percent confidence intervals of Cmax ratios were 0.7921, 1.0134 (ratio 0.8960) and 0.8246, 1.1199 (ratio 0.9610) for generic A and B vs. branded amoxicillin, respectively. The mean pharmacokinetic profiles showed that the AUC value of branded amoxicillin was 8.5 and 5.4% greater than that estimated for generic A and B, respectively. Few adverse events were recorded; these were not serious and occurred without apparent relationship to any specific amoxicillin formulation.

CONCLUSIONS

These results indicate that one of the two marketed amoxicillin generics analysed in the present study is not bioequivalent to the brand leader product for Cmax on the basis of single‐dose pharmacokinetic assessment.
15‐lipoxygenase metabolites play an important role in the development of a T‐helper type 1 allergic inflammation induced by double‐stranded RNA
Authors: Jeon S. G. , Moon H.‐G. , Kim Y.‐S. , Choi J.‐P. , Shin T.‐S. , Hong S.‐W. , Tae Y.‐M. , Kim S.‐H. , Zhu Z. , Gho Y. S. , Kim Y.‐K.
Published: February 2009

Background
We recently demonstrated that the T‐helper type 1 (Th1) immune response plays an important role in the development of non‐eosinophilic inflammation induced by airway exposure of an allergen plus double‐stranded RNA (dsRNA). However, the role of lipoxygenase (LO) metabolites in the development of Th1 inflammation is poorly understood.

Objective
To evaluate the role of LO metabolites in the development of Th1 inflammation induced by sensitization with an allergen plus dsRNA.

Methods
A Th2‐allergic inflammation mouse model was created by an intraperitoneal injection of lipopolysaccharide‐depleted ovalbumin (OVA, 75 μg) and alum (2 mg) twice, and the Th1 model was created by intranasal application of OVA (75 μg) and synthetic dsRNA [10 μg of poly(I : C)] four times, followed by an intranasal challenge with 50 μg of OVA four times. The role of LO metabolites was evaluated using two approaches: a transgenic approach using 5‐LO−/− and 15‐LO−/− mice, and a pharmacological approach using inhibitors of cysteinyl leucotriene receptor‐1 (cysLTR1), LTB4 receptor (BLT1), and 15‐LO.

Results
We found that the Th1‐allergic inflammation induced by OVA+dsRNA sensitization was similar between 5‐LO−/− and wild‐type (WT) control mice, although Th2 inflammation induced by sensitization with OVA+alum was reduced in the former group. In addition, dsRNA‐induced Th1 allergic inflammation, which is associated with down‐regulation of 15‐hydroxyeicosateraenoic acids production, was not affected by treatment with cysLTR1 or BLT1 inhibitors, whereas it was significantly lower in 12/15‐LO−/− mice compared with WT control mice. Moreover, dsRNA‐induced allergic inflammation and the recruitment of T cells following an allergen challenge were significantly inhibited by treatment with a specific 15‐LO inhibitor (PD146176).

Conclusion
15‐LO metabolites appear to be important mediators in the development of Th1‐allergic inflammation induced by sensitization with an allergen plus dsRNA. Our findings suggest that the 15‐LO pathway is a novel therapeutic target for the treatment of virus‐associated asthma characterized by Th1 inflammation.
Lentiviral calnexin‐modified dendritic cells promote expansion of high‐avidity effector T cells with central memory phenotype
Authors: Wang Bei , Han Shuhong , Lien Lily , Chang Lung‐Ji
Published: February 2009

Dendritic cells (DCs) are key immune mediators for the education and activation of effector cytotoxic T lymphocytes (CTLs). Ex vivo manipulation of DCs is an attractive strategy in immunotherapy. The chaperone proteins are known to hold the keys to proper protein folding and antigen processing. However, little is known of the role of molecular chaperones in DC and T‐cell functions. We report that DCs expressing supraphysiological levels of calnexin, a chaperone protein, via lentiviral gene transfer stimulated the expansion of high‐avidity CTLs with increased central memory phenotype. Microarray RNA profiling and analyses of protein expression with flow cytometry and multiplex enzyme‐linked immunosorbent assay indicated that calnexin had a global effect on DCs with up‐regulation of immune modulatory signals including costimulatory molecules, cytokines, chemokines and adhesion molecules. Compared with unmodified DCs, calnexin‐DCs were capable of activating T cells to exhibit increased functional avidity associated with up‐regulation of CCR7 and costimulatory tumour necrosis factor receptor superfamily molecules. These findings demonstrate a prominent role of calnexin in optimizing DC immunity with potential for improving immunotherapy.
Seed mass, abundance and breeding system among tropical forest species: do dioecious species exhibit compensatory reproduction or abundances?
Authors: Queenborough Simon A. , Mazer Susan J. , Vamosi Steven M. , Garwood Nancy C. , Valencia Renato , Freckleton Rob P.
Published: February 2009

Dioecious species may suffer a reproductive handicap compared to sympatric cosexual (hermaphroditic or monoecious) species of equal abundance simply because populations of dioecious species contain fewer seed‐producing individuals. To compensate for this population‐level disadvantage, natural selection in dioecious populations should favour females that reallocate those reproductive resources, that in cosexual individuals are invested in male function, towards the production of higher quality or more seeds, potentially leading to a higher density of established individuals.

We tested for two compensatory fitness advantages (heavier seeds and higher population densities) in dioecious species in the flora of a high‐diversity tropical forest in Western Amazonia. Using a phylogenetically corrected generalized linear modelling approach, we examined the phylogenetic dependence (Pagel's λ) of seed mass, abundance, growth form and wood‐specific gravity for 641 species from Yasuní National Park, Ecuador. Seed mass was highly correlated with phylogeny, but abundance was not. We then used AIC values to test for models (including breeding system) that best explained seed mass and species abundance, using the maximum likelihood values of λ.

Contrary to expectations, dioecious species exhibited no advantage with respect to either seed mass or population density; there was no difference in mean seed mass or abundance between dioecious species and their most closely related cosexual species.

We compared our results with those from a similar forest in the Tambopata Wildlife Reserve, Peru. There, dioecious shrubs had larger seeds than hermaphroditic shrubs, but (as for Yasuní) there was no difference between breeding systems in seed size among trees. Differences in the composition of species sampled may have contributed to differences in the results between the two sites.

We suggest that other individual fitness advantages, such as reduced inbreeding, increased dispersal, superior seed quality (e.g. better defences) or increased seed number contribute to the persistence of dioecious populations at Yasuní.

Synthesis. Similarities in the statistical models of seed mass and abundance for plant species in a Western Amazonian rain forest indicate that selective pressures on the seed‐producing individuals are similar, despite variation in sexual system. Therefore, breeding system may play a more limited role in community assembly of tropical forests than was previously considered.
Transient elastography and other noninvasive tests to assess hepatic fibrosis in patients with viral hepatitis
Authors: Castera Laurent
Published: February 2009

Summary.  The limitations of liver biopsy (invasive procedure, sampling errors, inter‐observer variability and nondynamic fibrosis evaluation) have stimulated the search for noninvasive approaches for the assessment of liver fibrosis in patients with viral hepatitis. A variety of methods including the measurement of liver stiffness, using transient elastography, and serum markers, ranging from routine laboratory tests to more complex algorithms or indices combining the results of panels of markers, have been proposed. Among serum indices, Fibrotest has been the most extensively studied and validated. Transient elastography appears as a promising method but has been mostly validated in chronic hepatitis C with performance equivalent to that of serum markers for the diagnosis of significant fibrosis. The combination of both approaches as first‐line assessment of liver fibrosis could avoid the performance of liver biopsy in the majority of patients with chronic hepatitis C, a strategy that deserves further evaluation in patients with hepatitis B or HIV‐HCV coinfection. Transient elastography also appears to be an excellent tool for early detection of cirrhosis and may have prognostic value in this setting. Guidelines are now awaited for the use of noninvasive methods in clinical practice.
The MYB transcription factor GhMYB25 regulates early fibre and trichome development
Authors: Machado Adriane , Wu Yingru , Yang Youming , Llewellyn Danny J. , Dennis Elizabeth S.
Published: February 2009

Little is still known about the developmental control of the long seed coat trichomes of cotton (Gossypium hirsutum L.). In Arabidopsis, leaf trichome initiation is regulated by a group of well‐defined transcription factors that includes MYB and homeodomain types. Many MYBs are expressed in fibres, but their roles in fibre development remain unclear. We analysed the function of one MYB transcription factor, GhMYB25, identified from transcriptome comparisons between wild‐type and fibreless cotton mutants. A GhMYB25 promoter‐GUS construct in transgenic cotton was expressed in the epidermis of ovules, developing fibre initials and fibres, in the trichomes of a number of tissues including leaves, stems and petals, as well as in the anthers, pollen and the epidermal layers of roots and root initials, but not in root hairs. Cotton is an allotetraploid with two very similar GhMYB25 genes that were silenced by a single RNAi construct. GhMYB25‐silenced cotton showed alterations in the timing of rapid fibre elongation, resulting in short fibres, dramatic reductions in trichomes on other parts of the plant, and reductions in seed production. Reciprocal crosses between transgenic and non‐transgenic plants indicated that pollen and ovule viability per se were not disrupted. Ectopic over‐expression of GhMYB25 had more subtle impacts, with increases in cotton fibre initiation and leaf trichome number. High expression appeared to adversely affect fertility. Our results provide convincing evidence for a role of GhMYB25, like other MIXTA‐like MYBS, in regulating specialized outgrowths of epidermal cells, including, in this case, cotton fibres.
Macroscopic Anatomy of the Ringed Seal [Pusa (Phoca) hispida] Lower Respiratory System
Authors: Smodlaka H. , Henry R. W. , Reed R. B.
Published: February 2009

This investigation serves to document the normal anatomical features of the lower respiratory tract of the ringed seal [Pusa (phoca) hispida]. Evaluation of embalmed specimens and tracheobronchial casts showed that the right lung of this seal consists of four lobes while the left has only three lobes. The ventral margins of the lungs do not reach the sternum causing them to form the boundary of the broad recessus costomediastinalis. Lung lobation corresponds with bronchial tree division. Pulmonary venous drainage includes right and left common veins draining ipsilateral cranial and middle lung lobes, and one common caudal vein draining both caudal lobes and the accessory lobe. The right and left pulmonary arteries divide into cranial and caudal branches at the level of the principal bronchus. The ringed seal has three tracheobronchial lymph nodes. The trachea has an average of 87 cartilages that exhibit a pattern of random anastomoses between adjacent rings. The trachea exhibits to a small degree the dorsoventrally flattened pattern that is described in other pinnipeds. The tracheal diameter is smaller than that of the canine.
New Public Management: The Cruellest Invention of the Human Spirit?1
Authors: LAPSLEY IRVINE
Published: February 2009

This article examines one of the most significant phenomena of the late twentieth and early twenty‐first centuries—the emergence of New Public Management (NPM). NPM has been widely adopted, internationally. However, its adoption is based on governments having faith in its deployment to transform their public sectors using private sector performance criteria. In this article, the case is advanced that the widespread use of NPM is often a cruel disappointment for governments. This is demonstrated by focusing on four key elements of NPM, as practised in the early twenty‐first century—the role of management consultants, the development of e‐government, the emergence of the ‘audit society’ and the increasing importance of risk management.
Self‐Fulfilling Prophecies of Failure: The Endogenous Balance Sheets of Distressed Companies
Authors: MEEKS G. , MEEKS J. G.
Published: February 2009

This article analyses a problem at the intersection of accounting, law, and economics: the economically efficient operation of legal arrangements for company failure is undermined because valuations of assets and liabilities become unstable once a firm is distressed. The paper draws on the three disciplines to show the pivotal role of asset and liability valuations in answering the legal question, whether the firm is insolvent, and the economic question, whether the firm should fail and its assets be redeployed to an alternative use. U.S. and U.K. evidence reveals a disconcerting indeterminacy in these processes: the probability that a firm will fail affects significantly the valuations assigned to assets and liabilities; but at the same time the valuation of assets and liabilities itself determines the probability of failure. This balance sheet endogeneity is then shown to delay economically efficient management changes under debtor‐oriented U.S. Chapter 11, and to induce unnecessary costly bankruptcy with creditor‐oriented U.K. receivership/administration. Recent cases trace this endogeneity in failures involving often controversial countermanding of huge financial claims.
Capital Project Analysis When Cash Flows Evolve as a Continuous Time Branching Process
Authors: DAVIDSON IAN , SHINOZAWA YOSHIKATSU , TIPPETT MARK
Published: February 2009

Optimal capital budgeting criteria now exist for a variety of applications when project cash flows (or present values) evolve in terms of the well‐known geometric Brownian motion. However, relatively little is known about the capital budgeting procedures that ought to be implemented when cash flows are generated by stochastic processes other than the geometric Brownian motion. Given this, our purpose here is to develop optimal investment criteria for capital projects with cash flows that evolve in terms of a continuous time branching process. Branching processes are compatible with an empirical phenomenon known as ‘volatility smile’. This occurs when there are systematic fluctuations in the implied volatility of a capital project's cash flows as the cash flow grows in magnitude. A number of studies have shown that this phenomenon characterizes the cash flow streams of the capital projects in which firms typically invest. We implement optimal capital budgeting procedures for both the continuous time branching process and the geometric Brownian motion using cost and revenue data for the Stuart oil shale project in central Queensland, Australia. This example shows that significant differences can arise between the optimal investment criteria for cash flows based on a branching process and those based on the geometric Brownian motion. This underscores the need for the geometric Brownian motion broadly to reflect the way a given capital project's cash flows actually evolve if serious errors in valuation and/or capital budgeting decisions are to be avoided.
Bayesian Fraud Risk Formula for Financial Statement Audits
Authors: SRIVASTAVA RAJENDRA P. , MOCK THEODORE J. , TURNER JERRY L.
Published: February 2009

In this article we extend the work of Loebbecke et al. (1989) and illustrate the use of an evidential reasoning approach for developing fraud risk analysis models under the Bayesian framework. New formulations facilitating fraud risk assessments are needed because decision tree approaches previously used to develop analytical models are not appropriate in complex situations involving several interrelated variables.

To demonstrate the evidential reasoning approach, a fraud risk assessment formula is derived and illustrated. The fraud risk formula captures the impact of the presence or absence of and interrelationships between the three ‘fraud triangle’ risk factors: Incentives, Attitude and Opportunities. The formula includes the impact of risks and controls related to these three fraud risk factors as well as the impact of forensic audit procedures and relevant analytical and other procedures that provide evidence for the presence or absence of fraud. This formula may be used in audit practice both to help plan the audit and to assess fraud risk sequentially as audit evidence is obtained.
Consistency, Value Relevance and Sufficiency of Book for Market Values in Five Japanese Conglomerates Over the Period 1950–2004
Authors: COOKE TERENCE , OMURA TERUYO , WILLETT ROGER
Published: February 2009

Market and accounting data for five Japanese conglomerates, Toyota, Fuji, Sony, Itochu and Sumitomo, are analysed over the period 1950 to 2004. Annual market value is regressed on three accounting and six macroeconomic variables, using a general‐to‐specific approach to construct simple error correction models for each of the five firms. The results show that in four of the five firms there is evidence of a long‐run relationship between market value and the net book value of assets, which can be interpreted, with increasing degrees of strength, as book values being either consistent with, value relevant for, or sufficient for market value.
Path Dependency and Comparative Industrial Relations: The Case of Conflict Resolution Systems in Ireland and Sweden
Authors: Teague Paul
Published: February 2009

This article uses the theory of path dependency to explain the evolution of employment conflict resolution systems in Ireland and Sweden. It argues that the traditional ‘voluntarist’ conflict management path followed in Ireland has fragmented as a result of a series of internal developments that have reduced trade union density, increased the importance of employment law in the settlement of workplace disputes and established social partnership as the main wage‐setting mechanism. By contrast, the Swedish system has experienced reform within the boundaries of the established conflict management path, which is largely attributable to the still powerful role played by trade unions within the country. Thus, while the operating rules of the system have changed, its core underlying principles — collectivism and self‐regulation — remain intact.
Dominance Effects from Local Competitors: Setting Institutional Parameters for Employment Relations in Multinational Subsidiaries; a Case from the Spanish Supermarket Sector
Authors: Royle Tony , Ortiz Luis
Published: February 2009

Dominance effects are normally associated with multinational corporations (MNCs). However, we argue that a strong local competitor can create ‘dominance effects’ setting the institutional parameters for employment relations in multinational subsidiaries. Moreover such an effect can be persistent. In this case the Spanish‐owned El Corte Inglés (ECI) used its power and influence to establish an employer's federation and two ‘yellow unions’. These yellow unions infiltrated the French‐owned MNC Carrefour and most of the Spanish supermarket sector by the early 1980s and continue to dominate collective bargaining rounds and works council elections, marginalizing the main independent trade unions. This has resulted in poor pay and working conditions and a lack of effective employee representation across most of the Spanish supermarket sector. The fact that Carrefour established an international framework agreement to observe union rights in 2001 has as yet not changed this situation.