bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and distribution of genetic markers in three closely related taxa of the Mycoplasma mycoides cluster: refining the relative position and boundaries of the Mycoplasma sp. bovine group 7 taxon (Mycoplasma leachii)
Authors: Tardy Florence , Maigre Laure , Poumarat François , Citti Christine
Published: October 2009

Mycoplasmas belonging to theMycoplasma mycoidesphylogenetic cluster are all important ruminant pathogens that are genetically closely related but differ in terms of severity and prevalence of the associated diseases. They are distributed among six taxa, the description of which has recently been amended. In the present study, DNA fragments that diverge between the type strains of three taxa were enriched using suppression subtractive hybridization. Of the three taxa, two were representative of the well-established speciesM. mycoidesandM. capricolum, while the third one,Mycoplasmasp. bovine group 7 (Mbg7), has only recently been proposed as a separate species,Mycoplasma leachii. Specific DNA fragments were further characterized by sequencing and used as markers to assess the genetic diversity within and between taxa. The data indicate that the selected markers are unequally distributed within their own taxon but also across taxa. The patterns observed suggest the occurrence of a genetic continuum of strains within theM. mycoidescluster that may compromise the boundaries between taxa and, in turn, diagnosis outcomes. ForMbg7, the overall nature and distribution of the markers indicate a rather homogeneous group that is distinct from theM. capricolumandM. mycoidesspecies and might be considered as a genomic chimera between these two species.
Influence of heterologous MreB proteins on cell morphology of Bacillus subtilis
Authors: Schirner Kathrin , Errington Jeff
Published: October 2009

The prokaryotic cytoskeletal protein MreB is thought to govern cell shape by positioning the cell wall synthetic apparatus at growth sites in the cell. In rod-shaped bacteria it forms helical filaments that run around the periphery of the rod during elongation. Gram-positive bacteria often contain more than one mreB gene. Bacillus subtilis has three mreB-like genes, mreB, mbl and mreBH, the first two of which have been shown to be essential under normal growth conditions. Expression of an mreB homologue from the closely related organism Bacillus licheniformis did not have any effect on cell growth or morphology. In contrast, expression of mreB from the phylogenetically more distant bacterium Clostridium perfringens produced shape defects and ultimately cell death, due to disruption of the endogenous MreB cytoskeleton. However, expression of either mreBB. licheniformis
(mreBBl
) or mreBC. perfringens
(mreBCp
) was sufficient to confer a rod shape to B. subtilis deleted for the three mreB isologues, supporting the idea that the three proteins have largely redundant functions in cell morphogenesis. Expression of mreBCDBl
could fully compensate for the loss of mreBCD in B. subtilis and led to the formation of rod-shaped cells. In contrast, expression of mreBCDCp
was not sufficient to confer a rod shape to B. subtilis ΔmreBCD, indicating that a complex of these three cell shape determinants is not enough for cell morphogenesis of B. subtilis.
Positive regulation of flhDC expression by OmpR in Yersinia pseudotuberculosis
Authors: Hu Yangbo , Wang Yao , Ding Lisha , Lu Pei , Atkinson Steve , Chen Shiyun
Published: October 2009

OmpR has been demonstrated to negatively regulate the expression of the flagellar master operon flhDC in a wide variety of bacterial species. Here we report the positive regulation of flhDC expression by OmpR in Yersinia pseudotuberculosis. A σ
70-dependent promoter was identified by primer extension analysis and an active region with two conserved OmpR-binding sites around the flhDC promoter was confirmed. To confirm the regulation of flhDC expression by OmpR, flhDC as well as the downstream flagellar genes fliA, flgD, flgA, flgM, fliC and flaA were fused to lacZ, and decreased expression of all these genes in an ompR mutant (ΔompR) was detected. Furthermore, ΔompR was defective in bacterial motility and flagella synthesis. This defect was due to the low level of expression of flhDC in ΔompR since overproduction of FlhDC in ΔompR restored bacterial motility. The importance of two conserved OmpR-binding sites around the flhDC promoter region in the regulation of flhDC expression by OmpR was demonstrated by the fact that mutation of either one or both sites significantly decreased the promoter activity in the wild-type but not in ΔompR. The binding of OmpR to these two sites was also demonstrated by DNA mobility shift assay. The possible mechanism underlying this positive regulation in Y. pseudotuberculosis is discussed. To our knowledge, this is the first report to demonstrate that OmpR positively regulates flhDC expression.
Gene cloning and characteristics of the RND-type multidrug efflux pump MuxABC-OpmB possessing two RND components in Pseudomonas aeruginosa
Authors: Mima Takehiko , Kohira Naoki , Li Yang , Sekiya Hiroshi , Ogawa Wakano , Kuroda Teruo , Tsuchiya Tomofusa
Published: October 2009

muxA-muxB-muxC-opmB (formerly PA2528-PA2527-PA2526-opmB), encoding a putative resistance nodulation cell division (RND)-type multidrug efflux pump system, was cloned from Pseudomonas aeruginosa PAO1. Introduction of muxABC-opmB into P. aeruginosa YM64, a drug-hypersusceptible strain, led to elevated MICs of aztreonam, macrolides, novobiocin and tetracycline. Since muxB and muxC, both of which encode RND components, were essential for function, MuxABC-OpmB is thought to be a drug efflux pump with four components. One novobiocin-resistant mutant, PMX725, isolated from P. aeruginosa PMX7 showed elevated resistance not only to novobiocin but also to aztreonam, macrolides and tetracycline. Increased mRNA expression of muxABC-opmB was observed in the mutant PMX725 compared with the parental strain. Sequencing analysis revealed that a single-nucleotide insertion had occurred in the deduced promoter region for muxABC-opmB in PMX725. In this study, we have characterized the last RND-type multidrug efflux pump predicted from the genome sequence in P. aeruginosa.
Influence of a model human defensive peroxidase system on oral streptococcal antagonism
Authors: Ashby Michael T. , Kreth Jens , Soundarajan Muthu , Sivuilu Laure Sita
Published: October 2009

Streptococcusis a dominant genus in the human oral cavity, making up about 20 % of the more than 800 species of bacteria that have been identified, and about 80 % of the early biofilm colonizers. Oral streptococci include both health-compatible (e.g.Streptococcus gordoniiandStreptococcus sanguinis) and pathogenic strains (e.g. the cariogenicStreptococcus mutans). Because the streptococci have similar metabolic requirements, they have developed defence strategies that lead to antagonism (also known as bacterial interference).S. mutansexpresses bacteriocins that are cytotoxic towardS. gordoniiandS. sanguinis, whereasS. gordoniiandS. sanguinisdifferentially produce H2O2(under aerobic growth conditions), which is relatively toxic towardS. mutans. Superimposed on the inter-bacterial combat are the effects of the host defensive mechanisms. We report here on the multifarious effects of bovine lactoperoxidase (bLPO) on the antagonism betweenS. gordoniiandS. sanguinisversusS. mutans. Some of the effects are apparently counterproductive with respect to maintaining a health-compatible population of streptococci. For example, the bLPO system (comprised of bLPO+SCN−+H2O2) destroys H2O2, thereby abolishing the ability ofS. gordoniiandS. sanguinisto inhibit the growth ofS. mutans. Furthermore, bLPO protein (with or without its substrate) inhibits bacterial growth in a biofilm assay, but sucrose negates the inhibitory effects of the bLPO protein, thereby facilitating adherence ofS. mutansin lieu ofS. gordoniiandS. sanguinis. Our findings may be relevant to environmental pressures that select early supragingival colonizers.
Identification and characterization of a novel spore-associated subtilase from Thermoactinomyces sp. CDF
Authors: Cheng Guyue , Zhao Peiwei , Tang Xiao-Feng , Tang Bing
Published: October 2009

A gene encoding a spore-associated subtilase, designated protease CDF, was cloned fromThermoactinomycessp. CDF and expressed inEscherichia coli. The enzyme gene is translated as a proform consisting of a 94 aa propeptide and a 283 aa mature protease domain. Phylogenetic analysis revealed that this enzyme belonged to the subtilisin family, but could not be grouped into any of its six known subfamilies. The mature protease CDF has an unusually high content of charged residues, which are mainly distributed on the enzyme surface. The recombinant proform of protease CDF formed inclusion bodies, but could be efficiently converted to the mature enzyme when the inclusion bodies were dissolved in alkaline buffers. The proform underwent a two-step maturation process, wherein the N-terminal part (85 residues) of the propeptide was autoprocessed intramolecularly, and the remaining 9-residue peptide was further processed intermolecularly. Protease CDF exhibited optimal proteolytic activity at 50–55 °C and pH 10.5–11.0. The enzyme was stable under high-pH conditions (pH 11.0–12.0), and NaCl could stabilize the enzyme at lower pH values. In addition, the enzyme was not dependent on calcium for either maturation or stability. By immunoblot analysis, protease CDF was found to be associated with spores, and could be extracted from the spores with 2 M KCl and alkaline buffers without damaging the coat layer, demonstrating that the protease CDF is located on the surface of the spore coat.
Alternative isoleucine synthesis pathway in cyanobacterial species
Authors: Wu Bing , Zhang Baichen , Feng Xueyang , Rubens Jacob R. , Huang Rick , Hicks Leslie M. , Pakrasi Himadri B. , Tang Yinjie J.
Published: October 2009

Cyanothece sp. ATCC 51142 is an aerobic N2-fixing and hydrogen-producing cyanobacterium. Isotopomer analysis of its amino acids revealed an identical labelling profile for leucine and isoleucine when Cyanothece 51142 was grown mixotrophically using 2-13C-labelled glycerol as the main carbon source. This indicated that Cyanothece 51142 employs the atypical alternative citramalate pathway for isoleucine synthesis, with pyruvate and acetyl-CoA as precursors. Utilization of the citramalate pathway was confirmed by an enzyme assay and LC-MS/MS analysis. Furthermore, the genome sequence of Cyanothece 51142 shows that the gene encoding the key enzyme (threonine ammonia-lyase) in the normal isoleucine pathway is missing. Instead, the cce_0248 gene in Cyanothece 51142 exhibits 53 % identity to the gene encoding citramalate synthase (CimA, GSU1798) from Geobacter sulfurreducens. Reverse-transcription PCR indicated that the cce_0248 gene is expressed and its transcriptional level is lower in medium with isoleucine than in isoleucine-free medium. Additionally, a blast search for citramalate synthase and threonine ammonia-lyase implies that this alternative isoleucine synthesis pathway may be present in other cyanobacteria, such as Cyanothece and Synechococcus. This suggests that the pathway is more widespread than originally thought, as previous identifications of the citramalate pathway are limited to mostly anaerobic bacteria or archaea. Furthermore, this discovery opens the possibility that such autrotrophic micro-organisms may be engineered for robust butanol and propanol production from 2-ketobutyrate, which is an intermediate in the isoleucine biosynthesis pathway.
Identification and functional characterization of the iron-dependent regulator (IdeR) of Mycobacterium avium subsp. paratuberculosis
Authors: Janagama Harish K. , Senthilkumar T. M. A. , Bannantine John P. , Rodriguez G. Marcela , Smith Issar , Paustian Michael L. , McGarvey Jeffery A. , Sreevatsan Srinand
Published: October 2009

Mycobacterium avium subspecies paratuberculosis (MAP), the causative agent of Johne's disease in cattle and sheep, has unique iron requirements in that it is mycobactin-dependent for cultivation in vitro. The iron-dependent regulator (IdeR) is a well-characterized global regulator responsible for maintaining iron homeostasis in Mycobacterium tuberculosis (MTB). We identified an orthologous segment in the MAP genome, MAP2827, with >93 % amino acid identity to MTB IdeR. Electrophoretic mobility shift assays and DNase protection assays confirmed that MAP2827 binds the 19 bp consensus motif (iron box) on the MAP genome. Sequencing of MAP2827 from multiple isolates revealed a non-synonymous change (R91G) exclusive to sheep strains. Reporter gene assays and quantitative real-time RT-PCR assays in two diverse MAP strains and in an ideR deletion mutant of M. smegmatis (mc2155) suggested that both sheep MAP IdeR (sIdeR) and cattle MAP IdeR (cIdeR) repress mbtB transcription at high iron concentrations and relieve repression at low iron concentrations. On the other hand, bfrA (an iron storage gene) was upregulated by cIdeR when presented with MTB or the cattle MAP bfrA promoter, and was downregulated by sIdeR in the presence of MTB, or sheep or cattle MAP bfrA promoters, at high iron concentrations. The differential iron regulatory mechanisms between IdeR-regulated genes across strains may contribute to the differential growth or pathogenic characteristics of sheep and cattle MAP strains. Taken together, our study provides a possible reason for mycobactin dependency and suggests strong implications in the differential iron acquisition and storage mechanisms in MAP.
Multiple adhesin proteins on the cell surface of Streptococcus gordonii are involved in adhesion to human fibronectin
Authors: Jakubovics Nicholas S. , Brittan Jane L. , Dutton Lindsay C. , Jenkinson Howard F.
Published: October 2009

Adhesion of bacterial cells to fibronectin (FN) is thought to be a pivotal step in the pathogenesis of invasive infectious diseases. Viridans group streptococci such as Streptococcus gordonii are considered commensal members of the oral microflora, but are important pathogens in infective endocarditis. S. gordonii expresses a battery of cell-surface adhesins that act alone or in concert to bind host receptors. Here, we employed molecular genetic approaches to determine the relative contributions of five known S. gordonii surface proteins to adherence to human FN. Binding levels to FN by isogenic mutants lacking Hsa glycoprotein were reduced by 70 %, while mutants lacking CshA and CshB fibrillar proteins showed approximately 30 % reduced binding. By contrast, disruption of antigen I/II adhesin genes sspA and sspB in a wild-type background did not result in reduced FN binding. Enzymic removal of sialic acids from FN led to reduced S. gordonii DL1 adhesion (>50 %), but did not affect binding by the hsa mutant, indicating that Hsa interacts with sialic acid moieties on FN. Conversely, desialylation of FN did not affect adherence levels of Lactococcus lactis cells expressing SspA or SspB polypeptides. Complementation of the hsa mutant partially restored adhesion to FN. A model is proposed for FN binding by S. gordonii in which Hsa and CshA/CshB are primary adhesins, and SspA or SspB play secondary roles. Understanding the basis of oral streptococcal interactions with FN will provide a foundation for development of new strategies to control infective endocarditis.
Immunodeficiencies
Authors: Ballow M , Notarangelo L , Grimbacher B , Cunningham-Rundles C , Stein M , Helbert M , Gathmann B , Kindle G , Knight A K , Ochs H D , Sullivan K , Franco J L
Published: October 2009

Primary immunodeficiencies (PIDs) are uncommon, chronic and severe disorders of the immune system in which patients cannot mount a sufficiently protective immune response, leading to an increased susceptibility to infections. The treatment of choice for PID patients with predominant antibody deficiency is intravenous immunoglobulin (Ig) replacement therapy. Despite major advances over the last 20 years in the molecular characterization of PIDs, many patients remain undiagnosed or are diagnosed too late, with severe consequences. Various strategies to ensure timely diagnosis of PIDs are in place, and novel approaches are being developed. In recent years, several patient registries have been established. Such registries shed light on the pathology and natural history of these varied disorders. Analyses of the registry data may also reveal which patients are likely to respond well to higher Ig infusion rates and may help to determine the optimal dosing of Ig products. Faster infusion rates may lead to improved convenience for patients and thus increase patient compliance, and may reduce nursing time and the need for hospital resources. Data from two recent studies suggest that Gamunex® and Privigen® are well tolerated at high infusion rates. Nevertheless, careful selection of patients for high infusion rates, based on co-morbid conditions and tolerance of the current infusion rate, is advisable. Based on the available data, intravenous Ig offers broad protection against encapsulated organisms. As vaccine trends change, careful monitoring of specific antibody levels in the general population, such as those against pneumococcal and meningococcal bacteria, should be implemented.
Clinical applications of intravenous immunoglobulins (IVIg) – beyond immunodeficiencies and neurology
Authors: Hartung H-P , Mouthon L , Ahmed R , Jordan S , Laupland K B , Jolles S
Published: October 2009

The clinical use of intravenous immunoglobulin (IVIg) has expanded beyond its traditional place in the treatment of patients with primary immunodeficiencies. Due to its multiple anti-inflammatory and immunomodulatory properties, IVIg is used successfully in a wide range of autoimmune and inflammatory conditions. Recognized autoimmune indications include idiopathic thrombocytopenic purpura (ITP), Kawasaki disease, Guillain–Barré syndrome and other autoimmune neuropathies, myasthenia gravis, dermatomyositis and several rare diseases. Several other indications are currently under investigation and require additional studies to establish firmly the benefit of IVIg treatment. Increasing attention is being turned to the use of IVIg in combination with other agents, such as immunosuppressive agents or monoclonal antibodies. For example, recent studies suggest that combination therapy with IVIg and rituximab (an anti-CD20 monoclonal antibody) may be effective for treatment of autoimmune mucocutaneous blistering diseases (AMBDs), with sustained clinical remission. The combination of IVIg and rituximab has also been used in the setting of organ transplantation. Firstly, IVIg ± rituximab has been administered to highly human leucocyte antigen (HLA)-sensitized patients to reduce anti-HLA antibody levels, thereby allowing transplantation in these patients. Secondly, IVIg in combination with rituximab is effective in the treatment of antibody-mediated rejection following transplantation. Treatment with polyclonal IVIg is a promising adjunctive therapy for severe sepsis and septic shock, but its use remains controversial and further study is needed before it can be recommended routinely. This review covers new developments in these fields and highlights the broad range of potential therapeutic areas in which IVIg may have a clinical impact.
Natural antibodies, intravenous immunoglobulin and their role in autoimmunity, cancer and inflammation
Authors: Schwartz-Albiez R , Monteiro R C , Rodriguez M , Binder C J , Shoenfeld Y
Published: October 2009

Natural antibodies are produced by B lymphocytes in the absence of external antigen stimulation. With their ability to recognize self, altered self and foreign antigens, they comprise an important first-line defence against invading pathogens, but are also important for tissue homeostasis. By recognizing oligosaccharides expressed on tumour cells and modified cell surface structures accompanying necrosis, natural antibodies have an important anti-tumorigenic function. IVIg contains a wide spectrum of specificities presented in normal plasma including natural antibodies and has been shown to exert inhibitory effects on tumour cells through a subfraction of anti-vascular endothelial growth factor immunoglobulin (Ig)G antibodies with anti-angiogenic properties. IgA antibodies also have potent immunomodulatory properties, being able to both induce and suppress immune responses. IgA-mediated inhibitory function is able to inhibit several inflammatory diseases including asthma and glomerulonephritis. Autoantibodies of the IgM type, on the other hand, have shown promising results in the treatment of multiple sclerosis. These autoantibodies promote remyelination rather than modulating inflammation. Oxidation-specific epitopes, as found in atherosclerotic lesions and on apoptotic cells, comprise one important target of natural antibodies. By recognizing these epitopes, natural antibodies neutralize proinflammatory responses and mediate atheroprotection.
Postmarketing surveillance study of KOGENATE® Bayer with Bio‐Set® in patients with haemophilia A: evaluation of patients’ satisfaction after switch to the new reconstitution system
Authors: VIDOVIC N. , MUSSO R. , KLAMROTH R. , ENRIQUEZ M. M. , ACHILLES K.
Published: October 2009

Summary.  KOGENATE® Bayer (rFVIII‐FS) with Bio‐Set® is designed to prevent patient contact with exposed needles during recombinant factor VIII reconstitution. This postmarketing surveillance study evaluated patient satisfaction before and after switching to the new Bio‐Set reconstitution method. Male children and adults with haemophilia A were enrolled from nine European countries. A preference questionnaire was administered to patients after Bio‐Set training and at the end of the observation period (≥20 exposure days or 3 months). Physician assessments of patient compliance and satisfaction were conducted at the end of the observation period. Patients (N = 306) received a mean ± SD of 28 ± 23 infusions of rFVIII‐FS with Bio‐Set. A majority of patients (82%) preferred the Bio‐Set method, with domain scores for ease of use, safety from needlesticks, and speed of reconstitution being highest after training and at the end of the observation period. The Bio‐Set method received higher mean scores than previous reconstitution methods for worry/safety and ease/confidence domains at both time points. Physician‐reported patient compliance with the Bio‐Set method was similar or greater compared with the previous method for 94% of the patients, with physicians reporting that 92% of the patients were satisfied or very satisfied with Bio‐Set. Thirteen adverse events (AEs) occurred in nine patients, and five serious AEs occurred in five patients; none was related to rFVIII‐FS. No de novo or recurrent inhibitor development was observed during the observation period. rFVIII‐FS with Bio‐Set was well tolerated and well accepted by haemophilia A patients, which may improve treatment compliance.
A ferric chloride induced arterial injury model used as haemostatic effect model
Authors: MØLLER F. , TRANHOLM M.
Published: October 2009

Summary.  A number of experimental bleeding models have been applied to animal models of haemophilia in order to evaluate the acute haemostatic effect of procoagulant compounds. In contrast, in vivo thrombosis models (including the FeCl3 induced injury model) have mainly been used to study antithrombotic pharmacological intervention. However, as there are limitations to existing bleeding models and as new recombinant FVIII, FIX, and FVIIa variants with increased and prolonged activity are generated there is an increasing need for new and optimized in vivo animal models for testing the efficacy of these haemostatic drug candidates. This led us to look at existing thrombosis models in a new perspective. We have studied the effect of a FeCl3 induced arterial injury in both F8‐KO and F9‐KO mice using optimized conditions where exposure to FeCl3 induces occlusion within 4.2 ± 0.2 min in wild type mice with a normal coagulation system. In contrast, no occlusion was observed in haemophilic mice providing a therapeutic window in the model making it suitable for pharmacological testing of therapeutic intervention. We demonstrate that replacement therapy with a clinical relevant dose of rFVIII (Advate® 20–80 U kg−1) and rFIX [(0.75 mg kg−1 BeneFIX®) ∼50 IU kg−1] restored coagulation and normalized the time to occlusion following FeCl3 induced injury in F8‐KO mice and restored coagulation and nearly normalized the time to occlusion in F9‐KO mice. In conclusion, we have demonstrated that under optimized conditions the FeCl3 induced arterial injury model provides a therapeutic window that makes it an useful effect model for evaluation of the haemostatic potential of procoagulant drugs.
Idiopathic male infertility is strongly associated with aberrant methylation of MEST and IGF2/H19 ICR1
Authors: Poplinski A. , Tüttelmann F. , Kanber D. , Horsthemke B. , Gromoll J.
Published: October 2009

Aberrant imprinting in spermatozoa in a subset of infertile men has been postulated to be a risk factor for congenital diseases in children conceived via assisted reproduction techniques (ART). Studies in clinically well characterized large cohorts, however, have been missing. Using bisulfite sequencing, we determined the degree of methylation of the IGF2/H19 imprinting control region 1 (ICR1) and MEST differentially methylated regions in swim‐up purified spermatozoa from 148 idiopathic infertile men and 33 normozoospermic controls. All control individuals had a high degree of IGF2/H19 ICR1 and a low degree of MEST methylation. Low sperm counts were clearly associated with IGF2/H19 ICR1 hypomethylation and, even stronger, with MEST hypermethylation. MEST hypermethylation, but not IGF2/H19 ICR1 hypomethylation was found in idiopathic infertile men with progressive sperm motility below 40% and bad sperm morphology below 5% normal spermatozoa. Ageing could be ruled out as a cause for the observed methylation defects. Sequence analysis of the CTCFL gene in peripheral blood DNA from 20 men with severe methylation defects revealed several polymorphisms, but no bona fide mutation. We conclude that idiopathic male infertility is strongly associated with imprinting defects at IGF2/H19 ICR1 and MEST, with aberrant MEST methylation being a strong indicator for sperm quality. The male germ cell thus represents a potential source for aberrant epigenetic features in children conceived via ART.
In vitro markers for virulence in Yersinia ruckeri
Authors: Tobback E , Decostere A , Hermans K , Van den Broeck W , Haesebrouck F , Chiers K
Published: October 2009

In this study, different traits that have been associated with bacterial virulence were studied in Yersinia ruckeri. Two isolates that had been shown to cause disease and mortality in experimentally infected rainbow trout were compared with five avirulent isolates. Both virulent isolates showed high adhesion to gill and intestinal mucus of rainbow trout, whereas the majority of non‐virulent strains demonstrated significantly lower adhesion. A decrease in adherence capability following bacterial treatment with sodium metaperiodate and proteolytic enzymes suggested the involvement of carbohydrates and proteins. All strains were able to adhere to and invade chinook salmon embryo cell line (CHSE‐214), fathead minnow epithelial cell line (FHM) and rainbow trout liver cell line (R1). One non‐virulent strain was highly adhesive and invasive in the three cell lines, whereas the virulent strains showed moderate adhesive and invasive capacity. The internalization of several isolates was inhibited by colchicine and cytochalasin‐D, suggesting that microtubules and microfilaments play a role. For all strains, intracellular survival assays showed a decrease of viable bacteria in the cells 6 h after inoculation, suggesting that Y. ruckeri is not able to multiply or survive inside cultured cells. Analysis of the susceptibility to the bactericidal effect of rainbow trout serum demonstrated that virulent Y. ruckeri strains were serum resistant, whereas non‐virulent strains were generally serum sensitive.
Correction of a bootstrap approach to testing for evolution along lines of least resistance
Authors: BERNER D.
Published: October 2009

Testing for an association between the leading vectors of multivariate trait (co)variation within populations (the ‘line of least resistance’) and among populations is an important tool for exploring variational bias in evolution. In a recent study of stickleback fish populations, a bootstrap‐based test was introduced that takes into account estimation error in both vectors and hence improves the previously available bootstrap method. Because this test was implemented incorrectly, however, I here describe the correct test protocol and provide a reanalysis of the original data set. The application of this new test protocol should improve future investigations of evolution along lines of least resistance and other vector comparisons.
Alternative reproductive tactics and the propensity of hybridization
Authors: TYNKKYNEN K. , RAATIKAINEN K. J. , HÄKKILÄ M. , HAUKILEHTO E. , KOTIAHO J. S.
Published: October 2009

One explanation for hybridization between species is the fitness benefits it occasionally confers to the hybridizing individuals. This explanation is possible in species that have evolved alternative male reproductive tactics: individuals with inferior tactics might be more prone to hybridization provided it increases their reproductive success and fitness. Here we experimentally tested whether the propensity of hybridization in the wild depends on male reproductive tactic in Calopteryx splendens damselflies. Counter to our expectation, it was males adopting the superior reproductive tactic (territoriality) that had greatest propensity to hybridize than males adopting the inferior tactics (sneakers and floaters). Moreover, among the territorial males, the most ornamented males had greatest propensity to hybridize whereas the pattern was reversed in the sneaker males. Our results suggest that there is fluctuating selection on male mate discrimination against heterospecific females depending on both ornament size and the male’s reproductive tactic.
Evidence for small scale variation in the vertebrate brain: mating strategy and sex affect brain size and structure in wild brown trout (Salmo trutta)
Authors: KOLM N. , GONZALEZ‐VOYER A. , BRELIN D. , WINBERG S.
Published: October 2009

The basis for our knowledge of brain evolution in vertebrates rests heavily on empirical evidence from comparative studies at the species level. However, little is still known about the natural levels of variation and the evolutionary causes of differences in brain size and brain structure within‐species, even though selection at this level is an important initial generator of macroevolutionary patterns across species. Here, we examine how early life‐history decisions and sex are related to brain size and brain structure in wild populations using the existing natural variation in mating strategies among wild brown trout (Salmo trutta). By comparing the brains of precocious fish that remain in the river and sexually mature at a small size with those of migratory fish that migrate to the sea and sexually mature at a much larger size, we show, for the first time in any vertebrate, strong differences in relative brain size and brain structure across mating strategies. Precocious fish have larger brain size (when controlling for body size) but migratory fish have a larger cerebellum, the structure in charge of motor coordination. Moreover, we demonstrate sex‐specific differences in brain structure as female precocious fish have a larger brain than male precocious fish while males of both strategies have a larger telencephalon, the cognitive control centre, than females. The differences in brain size and structure across mating strategies and sexes thus suggest the possibility for fine scale adaptive evolution of the vertebrate brain in relation to different life histories.
Chronic hepatitis C genotype 6 responds better to pegylated interferon and ribavirin combination therapy than genotype 1
Authors: Tsang Owen T‐Y , Zee Jonpaul S‐T , Chan Jacky M‐C , Li Reggie S‐T , Kan Yee‐Man , Li Francis T‐W , Lo Fu‐Hang , Chow David A , Cheung Kent W‐L , Chan Kam‐Hon , Yeung Yat‐Wah , Ng Fook‐Hong , Li Michael K‐K , Kwan Wai‐Keung , Lai Thomas S‐T
Published: October 2009

Background and Aims:  Chronic hepatitis C genotype 6 is common in Hong Kong, especially among i.v. drug abusers. Responses of these patients to combination of pegylated interferon and ribavirin treatment were inconsistent and the numbers of patients involved in previous studies were small. We performed a retrospective study to compare the therapeutic responses of this regimen in patients infected with genotype 6 and genotype 1.

Methods:  Seventy patients with either genotype 6 or genotype 1 were recruited. Both groups received 800–1200 mg of ribavirin daily plus either 180 mg of pegylated α‐interferon‐2a or 1.5 mg/kg pegylated α‐interferon‐2b weekly for 48 weeks. Their responses to treatments were compared.

Results:  The early virological response to combination therapy of patients with genotype 6 was significantly better than that of genotype 1 (88.6% vs 74.3%, P = 0.03). Significant difference was also identified in the end of treatment response of the two genotypes (60% vs 81.4% for genotype 1 and 6, respectively; P = 0.005). The sustained virological response (SVR) to treatment in patients with genotype 6 was also significantly superior to that of patients with genotype 1 (75.7% vs 57.1%, P = 0.02). Multiple logistic regression analysis demonstrated that age of 55 years or less, genotypes of hepatitis C virus, liver biopsy staging and baseline hepatitis C virus RNA of 200 000 IU/mL or less were independent predictors for better SVR in this cohort.

Conclusion:  Patients with chronic hepatitis C genotype 6 respond better to pegylated interferon and ribavirin combination treatment than patients with genotype 1.
Correlations among Helicobacter pylori infection and the expression of cyclooxygenase‐2 and vascular endothelial growth factor in gastric mucosa with intestinal metaplasia or dysplasia
Authors: Liu Dongping , He Qingjuan , Liu Caigang
Published: October 2009

Background and Aims:  To examine the rate of Helicobacter pylori infection and the expression of cyclooxygenase‐2 (COX‐2) and vascular endothelial growth factor (VEGF) in gastric mucosa with intestinal metaplasia or dysplasia, and explore their correlations in precancerous gastric lesions.

Methods:  A total of 172 patients were included in the study. H. pylori infection was evaluated by hematoxylin–eosin and modified Giemsa staining. The expression of COX‐2 and VEGF proteins was detected by immunohistochemistry.

Results:  The rates of H. pylori infection in gastric mucosal dysplasia (DYS), intestinal metaplasia in gastric mucosa (IM), chronic atrophic gastritis (CAG) and chronic superficial gastritis (CSG) patients were significant differences (P = 0.001). The average optical density (AOD) values of COX‐2 staining in CSG, CAG, IM and DYS patients were 13.81 ± 5.53, 45.28 ± 21.44, 73.67 ± 26.02 and 91.23 ± 45.11, respectively, with significant differences among CSG, CAG and IM patients (P = 0.037, 0.001 and 0.047 for CSG vs CAG, CSG vs IM and CAG vs IM, respectively). The expression level of VEGF in DYS patients was significantly higher than those in other patients (P = 0.001, 0.001 and 0.001 for DYS vs CSG, DYS vs CAG and DYS vs IM, respectively). The expression levels of COX‐2 in H. pylori‐positive IM, CAG and DYS patients were significantly higher than those in H. pylori‐negative counterparts (P = 0.043, 0.009, 0.001, respectively). Additionally, the expression level of COX‐2 was positively correlated with that of VEGF with the aggravation of gastric mucosal lesions (r = 0.640, P = 0.006).

Conclusion:  H. pylori infection might be able to induce the expression of COX‐2 in precancerous gastric lesions, which in turn upregulates the expression of VEGF.
Australian Indigenous adolescents with chronic conditions: Sociocultural context
Authors: McDonald Heather
Published: October 2009

Scant information is available in the health literature on Australian Indigenous adolescents with chronic conditions and disabilities. Little is known about how Indigenous adolescence differs from mainstream adolescence, or how Indigenous adolescents manage chronic conditions. Health services are encouraged to engage in information sharing with Indigenous clients and to develop a collaborative approach to chronic condition management as a way to improve outcomes.
Sclerosing angiomatoid nodular transformation of the spleen (SANT): Clinicopathological study of 10 cases with or without abdominal disseminated calcifying fibrous tumors, and the presence of a significant number of IgG4+ plasma cells
Authors: Kuo Tseng‐tong , Chen Tse‐Ching , Lee Li‐yu
Published: October 2009

Sclerosing angiomatoid nodular transformation (SANT) is a peculiar splenic vascular lesion that is characterized by marked stromal sclerosis and the presence of plasma cells, which shares histopathological features associated with IgG4‐related sclerosing disease. The cinicopathological features of 10 cases of SANT were reviewed and immunohistochemistry with IgG4 and IgG antibodies was performed. Nine other various splenic lesions served as controls. Five cases of SANT were found incidentally. Three cases of SANT had multiple tumors and five had associated abdominal disseminated calcifying fibrous tumors (CFT). IgG4+ plasma cells were found in all of the cases of SANT and in calcifying fibrous tumors. The densities of IgG4+ and IgG+ cells and the IgG4/IgG ratios were significantly higher in SANT than in control spleens (P= 0.001, 0.006, and 0.028, respectively). Serum IgG4 concentration was elevated in one case. In conclusion, SANT can occur either as a solitary or as multiple tumors. Frequent association with abdominal disseminated CFT simulating carcinomatosis was observed. A statistically significant number of IgG4+ plasma cells was found in all of the cases of SANT and the associated CFT. Whether they are related to the IgG4‐related sclerosing disease or not is debatable and warrants further investigation.
Clinicopathological features of syphilitic gastritis in Korean patients
Authors: Kim Kyungeun , Kim Eun Ju , Kim Mi‐Jung , Song Ho June , Lee Yoon‐Seon , Jung Kee Wook , Yu Eunsil
Published: October 2009

Syphilitic gastritis is difficult to diagnose without a history of syphilis, because endoscopic and microscopic findings can simulate gastric cancer or lymphoma. Herein are reported two cases of syphilitic gastritis and analysis of the clinicopathological characteristics of 11 cases in Korean subjects, including nine previously reported ones. The two present patients were 25‐ and 32‐year‐old men with epigastric pain. The gastroduodenoscopy features were similar: multiple erosive or ulcerative lesions in whole gastric mucosa. Microscopically, gastric mucosa contained severe chronic active gastritis involving submucosa with crypt abscesses, venulitis and granulomas, suggesting unusual infectious gastritis. Numerous spirochetes were identified on silver staining, and serological tests for syphilis were reactive in both patients. They were treated with benzathin penicillin, and follow‐up gastric biopsy specimens indicated non‐specific chronic gastritis without evidence of syphilis. Of the 11 Korean patients with syphilitic gastritis, six were female and five were male (mean age, 31.7 years). The most common symptom was epigastric pain and all patients had diffuse erosive, ulcerative or infiltrative lesions on gastroduodenoscopy. Syphilitic gastritis should be considered in young patients with epigastric pain who have diffuse gastric involvement such as erosion or shallow ulcer on endoscopy and unusually extensive chronic active gastritis on microscopy, even if the history of syphilis is not clear.
Age‐related EBV‐associated B‐cell lymphoproliferative disorders: Diagnostic approach to a newly recognized clinicopathological entity
Authors: Shimoyama Yoshie , Asano Naoko , Kojima Masaru , Morishima Satoko , Yamamoto Kazuhito , Oyama Takashi , Kinoshita Tomohiro , Nakamura Shigeo
Published: October 2009

EBV is prevalent among healthy individuals, and is implicated in numerous reactive and neoplastic processes in the immune system. The authors originally identified a series of senile or age‐related EBV‐associated B‐cell lymphoproliferative disorders (LPD) bearing a resemblance to immunodeficiency‐associated ones, which may be associated with immune senescence in the elderly and which are now incorporated into the 2008 World Health Organization lymphoma classification as EBV‐positive diffuse large B‐cell lymphoma (DLBCL) of the elderly. This newly described disease is pathologically characterized by a proliferation of atypical large B cells including Reed–Sternberg‐like cells with reactive components, which pose a diagnostic problem for pathologists. Clinically, this disease may present with lymphadenopathy, and is often extranodal, frequently involving the skin, gastrointestinal tract, or lung. Onset is usually after the age of 50; the median patient age is 70–79 years, and incidence continues to increase with age, providing additional support to the nosological term of EBV+ DLBCL of the elderly. These patients have a worse prognosis than those with EBV‐negative DLBCL or EBV+ classical Hodgkin lymphoma (CHL). The aim of the present review was to summarize the clinicopathological profile of age‐related EBV+ LPD and EBV+ Hodgkin lymphoma to facilitate diagnostic approach.
Prostate cancer incidence, stage at diagnosis, treatment and survival in ethnic groups in South‐East England
Authors: Jack Ruth H. , Davies Elizabeth A. , Møller Henrik
Published: October 2009

Study Type – Prevalence (prospective cohort) Level of Evidence 1b

OBJECTIVES

To use self‐assigned ethnicity to examine patterns of incidence, stage, treatment and survival in patients with prostate cancer in South‐east England.

PATIENTS AND METHODS

Data on 36 961 men resident in South‐east England and diagnosed with prostate cancer between 1998 and 2003 were extracted from the Thames Cancer Registry. Ethnicity information was obtained from the Hospital Episode Statistics dataset, and matched to the cancer records. The ethnic groups examined were White (19 688), Black (1422) and Indian/Pakistani (397). Age‐standardized incidence rate ratios were calculated overall and for narrower age groups, with White men as the baseline group. Logistic regression was used to assess whether patients had a stage of disease recorded at diagnosis, if so whether it was metastatic, and to examine treatment received. To assess overall and prostate cancer‐specific survival (PCSS), Cox regression models were fitted, adjusting sequentially for age, socioeconomic status, treatment received and stage of disease at diagnosis.

RESULTS

Indian/Pakistani men had a lower age‐standardized rate than White men (rate ratio 0.69, 95% confidence interval 0.63–0.75), while Black men had a higher rate ratio (2.51, 2.30–2.73). There was no difference in the proportion of men diagnosed with metastatic disease in each ethnic group. There was variation in recorded surgery and hormone treatment. Indian/Pakistani men had better PCSS than White men (fully adjusted hazard ratio 0.76, P = 0.024). There was no difference in PCSS between Black and White men (hazard ratio 0.93, P = 0.238).

CONCLUSIONS

Black men had the highest incidence of prostate cancer, followed by White, then Indian/Pakistani men. The relative excess of prostate cancer in Black vs White men was strongly age‐dependent. Despite differences in recorded treatment, Indian/Pakistani men had better overall survival and PCSS. Black men also had better overall survival, and their PCSS was similar to that of White men. This might be due to access to the publicly funded National Health Service in the UK.
Worldwide status of burbot and conservation measures
Authors: Stapanian Martin A , Paragamian Vaughn L , Madenjian Charles P , Jackson James R , Lappalainen Jyrki , Evenson Matthew J , Neufeld Matthew D
Published: October 2009

Although burbot (Lota lota Gadidae) are widespread and abundant throughout much of their natural range, there are many populations that have been extirpated, endangered or are in serious decline. Due in part to the species’ lack of popularity as a game and commercial fish, few regions consider burbot in management plans. We review the worldwide population status of burbot and synthesize reasons why some burbot populations are endangered or declining, some burbot populations have recovered and some burbot populations do not recover despite management measures. Burbot have been extirpated in much of Western Europe and the United Kingdom and are threatened or endangered in much of North America and Eurasia. Pollution and habitat change, particularly the effects of dams, appear to be the main causes for declines in riverine burbot populations. Pollution and the adverse effects of invasive species appear to be the main reasons for declines in lacustrine populations. Warmer water temperatures, due either to discharge from dams or climate change, have been noted in declining burbot populations at the southern extent of their range. Currently, fishing pressure does not appear to be limiting burbot populations world‐wide. We suggest mitigation measures for burbot population recovery, particularly those impacted by dams and invasive species.
Publications in mathematical economics and econometrics: ranking of Asian universities and an application of Zipf's law
Authors: Jin Jang C.
Published: October 2009

This paper ranks Asian universities in two related economics fields: mathematical economics and econometrics. Key findings are that Japanese universities dominate in mathematical economics, while Hong Kong universities are fairly evenly balanced in these two specialty areas of quantitative economics. The results of the analysis also show that Zipf's law applies to research‐based university rankings.
Gross national happiness
Authors: Bates Winton
Published: October 2009

This article considers the concept of gross national happinesss, as it has evolved in Bhutan, against the background of literature on the pursuit of happiness as a government objective and the problems associated with different approaches to measuring well‐being. It concludes that since all measures of well‐being are imperfect, including the measure of gross national happiness currently being applied in Bhutan, the best approach is to use a range of different measures, including conventional national accounting indicators.
Emigration in the long run: evidence from two global centuries
Authors: Hatton Timothy J. , Williamson Jeffrey G.
Published: October 2009

International migration in the last half century is often characterised as following an inexorable upward trend that can only be stemmed by tougher immigration policies in the rich OECD. This view fails to pay sufficient attention to the supply‐side forces that drive emigration from poor to rich countries. European mass migrations before 1914 suggest that emigration typically traces out what is sometimes called the ‘migration hump’ and what we call an ‘emigration life cycle’. This paper examines the forces that underlay the mass migration from pre‐1914 Europe and compares them with the experience since 1970. Despite the great importance of restrictive immigration policy today, we find the same forces at work in poor source countries today as a century ago. Our results also suggest that, contrary to popular belief, emigration pressure from the Third World is beginning to ease.