bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reactive Oxygen Species Contribute to the Bactericidal Effects of the Fluoroquinolone Moxifloxacin in Streptococcus pneumoniae
Authors: Ferrándiz M. J. , Martín-Galiano A. J. , Arnanz C. , Zimmerman T. , de la Campa A. G. 
Published: November 2015

ABSTRACTWe studied the transcriptomic response ofStreptococcus pneumoniaeto the fluoroquinolone moxifloxacin at a concentration that inhibits DNA gyrase. Treatment of the wild-type strain R6, at a concentration of 10× the MIC, triggered a response involving 132 genes after 30 min of treatment. Genes from several metabolic pathways involved in the production of pyruvate were upregulated. These included 3 glycolytic enzymes, which ultimately convert fructose 6-phosphate to pyruvate, and 2 enzymes that funnel phosphate sugars into the glycolytic pathway. In addition, acetyl coenzyme A (acetyl-CoA) carboxylase was downregulated, likely leading to an increase in acetyl-CoA. When coupled with an upregulation in formate acetyltransferase, an increase in acetyl-CoA would raise the production of pyruvate. Since pyruvate is converted by pyruvate oxidase (SpxB) into hydrogen peroxide (H2O2), an increase in pyruvate would augment intracellular H2O2. Here, we confirm a 21-fold increase in the production of H2O2and a 55-fold increase in the amount of hydroxyl radical in cultures treated during 4 h with moxifloxacin. This increase in hydroxyl radical through the Fenton reaction would damage DNA, lipids, and proteins. These reactive oxygen species contributed to the lethality of the drug, a conclusion supported by the observed protective effects of an SpxB deletion. These results support the model whereby fluoroquinolones cause redox alterations. The transcriptional response ofS. pneumoniaeto moxifloxacin is compared with the response to levofloxacin, an inhibitor of topoisomerase IV. Levofloxacin triggers the transcriptional activation of iron transport genes and also enhances the Fenton reaction.
All Three TonB Systems Are Required for Vibrio vulnificus CMCP6 Tissue Invasiveness by Controlling Flagellum Expression
Authors: Duong-Nu Tra-My , Jeong Kwangjoon , Hong Seol Hee , Nguyen Hong-Vu , Ngo Van-Hoan , Min Jung-Joon , Lee Shee Eun , Rhee Joon Haeng 
Published: November 2015

ABSTRACT

TonB systems actively transport iron-bound substrates across the outer membranes of Gram-negative bacteria.
Vibrio vulnificus
CMCP6, which causes fatal septicemia and necrotizing wound infections, possesses three active TonB systems. It is not known why
V. vulnificus
CMCP6 has maintained three TonB systems throughout its evolution. The TonB1 and TonB2 systems are relatively well characterized, while the pathophysiological function of the TonB3 system is still elusive. A reverse transcription-PCR (RT-PCR) study showed that the
tonB1
and
tonB2
genes are preferentially induced
in vivo
, whereas
tonB3
is persistently transcribed, albeit at low expression levels, under both
in vitro
and
in vivo
conditions. The goal of the present study was to elucidate the raison d'être of these three TonB systems. In contrast to previous studies, we constructed in-frame single-, double-, and triple-deletion mutants of the entire structural genes in TonB loci, and the changes in various virulence-related phenotypes were evaluated. Surprisingly, only the
tonB123
mutant exhibited a significant delay in killing eukaryotic cells, which was complemented in
trans
with any TonB operon. Very interestingly, we discovered that flagellum biogenesis was defective in the
tonB123
mutant. The loss of flagellation contributed to severe defects in motility and adhesion of the mutant. Because of the difficulty of making contact with host cells, the mutant manifested defective RtxA1 toxin production, which resulted in impaired invasiveness, delayed cytotoxicity, and decreased lethality for mice. Taken together, these results indicate that a series of virulence defects in all three TonB systems of
V. vulnificus
CMCP6 coordinately complement each other for iron assimilation and full virulence expression by ensuring flagellar biogenesis.
Interaction of Mycoplasma gallisepticum with Chicken Tracheal Epithelial Cells Contributes to Macrophage Chemotaxis and Activation
Authors: Majumder Sanjukta , Silbart Lawrence K. 
Published: November 2015

ABSTRACTMycoplasma gallisepticumcolonizes the chicken respiratory mucosa and mediates a severe inflammatory response hallmarked by subepithelial leukocyte infiltration. We recently reported that the interaction ofM. gallisepticumwith chicken tracheal epithelial cells (TECs) mediated the upregulation of chemokine and inflammatory cytokine genes in these cells (S. Majumder, F. Zappulla, and L. K. Silbart, PLoS One9:e112796,http://dx.doi.org/10.1371/journal.pone.0112796). The current study extends these observations and sheds light on how this initial interaction may give rise to subsequent inflammatory events. Conditioned medium from TECs exposed to the virulent Rlowstrain induced macrophage chemotaxis to a much higher degree than the nonvirulent Rhighstrain. Coculture of chicken macrophages (HD-11) with TECs exposed to live mycoplasma revealed the upregulation of several proinflammatory genes associated with macrophage activation, including interleukin-1β (IL-1β), IL-6, IL-8, CCL20, macrophage inflammatory protein 1β (MIP-1β), CXCL-13, and RANTES. The upregulation of these genes was similar to that observed upon direct contact of HD-11 cells with liveM. gallisepticum. Coculture of macrophages with Rlow-exposed TECs also resulted in prolonged expression of chemokine genes, such as those encoding CXCL-13, MIP-1β, RANTES, and IL-8. Taken together, these studies support the notion that the initial interaction ofM. gallisepticumwith host respiratory epithelial cells contributes to macrophage chemotaxis and activation by virtue of robust upregulation of inflammatory cytokine and chemokine genes, thereby setting the stage for chronic tissue inflammation.
Divergence between the Highly Virulent Zoonotic Pathogen Helicobacter heilmannii and Its Closest Relative, the Low-Virulence “Helicobacter ailurogastricus” sp. nov
Authors: Joosten Myrthe , Lindén Sara , Rossi Mirko , Tay Alfred Chin Yen , Skoog Emma , Padra Médea , Peters Fanny , Perkins Tim , Vandamme Peter , Van Nieuwerburgh Filip , D'Herde Katharina , Van den Broeck Wim , Flahou Bram , Deforce Dieter , Ducatelle Richard , Marshall Barry , Haesebrouck Freddy , Smet Annemieke 
Published: November 2015

ABSTRACT

Helicobacter heilmannii
naturally colonizes the stomachs of dogs and cats and has been associated with gastric disorders in humans. Nine feline
Helicobacter
strains, classified as
H. heilmannii
based on
ureAB
and 16S rRNA gene sequences, were divided into a highly virulent and a low-virulence group. The genomes of these strains were sequenced to investigate their phylogenetic relationships, to define their gene content and diversity, and to determine if the differences in pathogenicity were associated with the presence or absence of potential virulence genes. The capacities of these helicobacters to bind to the gastric mucosa were investigated as well. Our analyses revealed that the low-virulence strains do not belong to the species
H. heilmannii
but to a novel, closely related species for which we propose the name
Helicobacter ailurogastricus
. Several homologs of
H. pylori
virulence factors, such as IceA1, HrgA, and jhp0562-like glycosyltransferase, are present in
H. heilmannii
but absent in
H. ailurogastricus
. Both species contain a VacA-like autotransporter, for which the passenger domain is remarkably larger in
H. ailurogastricus
than in
H. heilmannii
. In addition,
H. ailurogastricus
shows clear differences in binding to the gastric mucosa compared to
H. heilmannii
. These findings highlight the low-virulence character of this novel
Helicobacter
species.
Reciprocal Regulation ofl-Arabinose andd-Xylose Metabolism in Escherichia coli
Authors: Koirala Santosh , Wang Xiaoyi , Rao Christopher V. 
Published: November 2015

ABSTRACTGlucose is known to inhibit the transport and metabolism of many sugars inEscherichia coli. This mechanism leads to its preferential consumption. Far less is known about the preferential utilization of nonglucose sugars inE. coli. Two exceptions arel-arabinose andd-xylose. Previous studies have shown thatl-arabinose inhibitsd-xylose metabolism inEscherichia coli. This repression results froml-arabinose-bound AraC binding to the promoter of thed-xylose metabolic genes and inhibiting their expression. This mechanism, however, has not been explored in single cells. Both thel-arabinose andd-xylose utilization systems are known to exhibit a bimodal induction response to their cognate sugar, where mixed populations of cells either expressing the metabolic genes or not are observed at intermediate sugar concentrations. This suggests thatl-arabinose can only inhibitd-xylose metabolism inl-arabinose-induced cells. To understand how cross talk between these systems affects their response, we investigatedE. coliduring growth on mixtures ofl-arabinose andd-xylose at single-cell resolution. Our results showed that mixed, multimodal populations ofl-arabinose- andd-xylose-induced cells occurred at intermediate sugar concentrations. We also found thatd-xylose inhibited the expression of thel-arabinose metabolic genes and that this repression was due to XylR. These results demonstrate that a strict hierarchy does not exist betweenl-arabinose andd-xylose as previously thought. The results may also aid in the design ofE. colistrains capable of simultaneous sugar consumption.IMPORTANCEGlucose,d-xylose, andl-arabinose are the most abundant sugars in plant biomass. Developing efficient fermentation processes that convert these sugars into chemicals and fuels will require strains capable of coutilizing these sugars. Glucose has long been known to repress the expression of thel-arabinose andd-xylose metabolic genes inEscherichia coli. Recent studies found thatl-arabinose also represses the expression of thed-xylose metabolic genes. In the present study, we found thatd-xylose also represses the expression of thel-arabinose metabolic genes, leading to mixed populations of cells capable of utilizingl-arabinose andd-xylose. These results further our understanding of mixed-sugar utilization and may aid in strain design.
Controlling the Connections of Cells to the Biofilm Matrix
Authors: Parsek Matthew R. 
Published: November 2015

ABSTRACT

The importance of cyclic di-GMP (c-di-GMP) and its control of biofilm matrix assembly and production has been a focal point of researchers in recent history. In this issue, Cooley et al. (Cooley RB, Smith TJ, Leung W, Tierney V, Borlee BR, O’Toole GA, Sondermann H, J Bacteriol 198:66–77,
http://dx.doi.org/10.1128/JB.00369-15
) demonstrate that two c-di-GMP controlled features of
Pseudomonas aeruginosa
, the periplasmic protease LapG and the surface adhesin CdrA, are linked. CdrA is shown to be a substrate of LapG, with LapG activity controlled by intracellular c-di-GMP levels. This commentary discusses the significance of this finding.
Contributions of maternal and paternal adiposity and smoking to adult offspring adiposity and cardiovascular risk: the Midspan Family Study
Authors: Han T S , Hart C L , Haig C , Logue J , Upton M N , Watt G C M , Lean M E J 
Published: November 2015

ObjectiveObesity has some genetic basis but requires interaction with environmental factors for phenotypic expression. We examined contributions of gender-specific parental adiposity and smoking to adiposity and related cardiovascular risk in adult offspring.DesignCross-sectional general population survey.SettingScotland.Participants1456 of the 1477 first generation families in the Midspan Family Study: 2912 parents (aged 45–64 years surveyed between 1972 and 1976) who had 1025 sons and 1283 daughters, aged 30–59 years surveyed in 1996.Main measuresOffspring body mass index (BMI), waist circumference (WC), cardiometabolic risk (lipids, blood pressure and glucose) and cardiovascular disease as outcome measures, and parental BMI and smoking as determinants. All analyses adjusted for age, socioeconomic status and family clustering and offspring birth weight.ResultsRegression coefficients for BMI associations between father–son (0.30) and mother–daughter (0.33) were greater than father–daughter (0.23) or mother–son (0.22). Regression coefficient for the non-genetic, shared-environment or assortative-mating relationship between BMIs of fathers and mothers was 0.19. Heritability estimates for BMI were greatest among women with mothers who had BMI either <25 or ≥30 kg/m2. Compared with offspring without obese parents, offspring with two obese parents had adjusted OR of 10.25 (95% CI 6.56 to 13.93) for having WC ≥102 cm for men, ≥88 cm women, 2.46 (95% CI 1.33 to 4.57) for metabolic syndrome and 3.03 (95% CI 1.55 to 5.91) for angina and/or myocardial infarct (p<0.001). Neither parental adiposity nor smoking history determined adjusted offspring individual cardiometabolic risk factors, diabetes or stroke. Maternal, but not paternal, smoking had significant effects on WC in sons (OR=1.50; 95% CI 1.13 to 2.01) and daughters (OR=1.42; 95% CI 1.10 to 1.84) and metabolic syndrome OR=1.68; 95% CI 1.17 to 2.40) in sons.ConclusionsThere are modest genetic/epigenetic influences on the environmental factors behind adverse adiposity. Maternal smoking appears a specific hazard on obesity and metabolic syndrome. A possible epigenetic mechanism linking maternal smoking to obesity and metabolic syndrome in offspring is proposed. Individuals with family histories of obesity should be targeted from an early age to prevent obesity and complications.
Understanding the motivation and performance of community health volunteers involved in the delivery of health programmes in Kampala, Uganda: a realist evaluation
Authors: Vareilles Gaëlle , Marchal Bruno , Kane Sumit , Petrič Taja , Pictet Gabriel , Pommier Jeanine 
Published: November 2015

ObjectivesThis paper presents the results of a realist evaluation that aimed to understand how, why and under what circumstances a Red Cross (RC) capacity-building intervention influences the motivation and the performance of RC community health volunteers involved in the delivery of an immunisation programme in Kampala, Uganda.MethodGiven the complexity of the intervention, we adopted realist evaluation as our methodological approach and the case study as our study design. Data collection included document review, participant observation and interviews. The constant comparative method was used for the analysis. Two contrasted cases were selected within the five Kampala districts. Each case covers the management of the immunisation programme implemented at a RC branch. In each case, a programme manager and 15 RC volunteers were interviewed. The selection of the volunteers was purposive.ResultsWe found that a capacity-building programme including supervision supportive of autonomy, skills and knowledge enhancement, and adapted to the different subgroups of volunteers, leads to satisfaction of the three key drivers of volunteer motivation: feelings of autonomy, competence and connectedness. This contributes to higher retention, and better task performance and well-being among the volunteers. Enabling contextual conditions include the responsiveness of the Uganda Red Cross Society (URCS) to community needs, and recognition of the work of the volunteers, from the URCS and the community.ConclusionsA management approach that caters for the different motivational states and changing needs of the volunteers will lead to better performance. The findings will inform not only the management of community health volunteers, but also the management of all kinds of health workers.
Prevalence, associated factors and heritabilities of metabolic syndrome and its individual components in African Americans: the Jackson Heart Study
Authors: Khan Rumana J , Gebreab Samson Y , Sims Mario , Riestra Pia , Xu Ruihua , Davis Sharon K 
Published: November 2015

ObjectiveBoth environmental and genetic factors play important roles in the development of metabolic syndrome (MetS). Studies about its associated factors and genetic contribution in African Americans (AA) are sparse. Our aim was to report the prevalence, associated factors and heritability estimates of MetS and its components in AA men and women.Participants and settingData of this cross-sectional study come from a large community-based Jackson Heart Study (JHS). We analysed a total of 5227 participants, of whom 1636 from 281 families were part of a family study subset of JHS.MethodsParticipants were classified as having MetS according to the Adult Treatment Panel III criteria. Multiple logistic regression analysis was performed to isolate independently associated factors of MetS (n=5227). Heritability was estimated from the family study subset using variance component methods (n=1636).ResultsAbout 27% of men and 40% of women had MetS. For men, associated factors with having MetS were older age, lower physical activity, higher body mass index, and higher homocysteine and adiponectin levels (p<0.05 for all). For women, in addition to all these, lower education, current smoking and higher stress were also significant (p<0.05 for all). After adjusting for covariates, the heritability of MetS was 32% (p<0.001). Heritability ranged from 14 to 45% among its individual components. Relatively higher heritability was estimated for waist circumference (45%), high density lipoprotein-cholesterol (43%) and triglycerides (42%). Heritability of systolic blood pressure (BP), diastolic BP and fasting blood glucose was 16%, 15% and 14%, respectively.ConclusionsStress and low education were associated with having MetS in AA women, but not in men. Higher heritability estimates for lipids and waist circumference support the hypothesis of lipid metabolism playing a central role in the development of MetS and encourage additional efforts to identify the underlying susceptibility genes for this syndrome in AA.
Bath additives for the treatment of childhood eczema (BATHE): protocol for multicentre parallel group randomised trial
Authors: Santer Miriam , Rumsby Kate , Ridd Matthew J , Francis Nick A , Stuart Beth , Chorozoglou Maria , Wood Wendy , Roberts Amanda , Thomas Kim S , Williams Hywel C , Little Paul 
Published: November 2015

IntroductionBath emollients are widely prescribed for childhood eczema, yet evidence of their benefits over direct application of emollients is lacking.ObjectivesTo determine the clinical and cost-effectiveness of adding bath emollient to the standard management of eczema in childrenMethods and analysisDesign: Pragmatic open 2-armed parallel group randomised controlled trial.Setting: General practitioner (GP) practices in England and Wales.Participants: Children aged over 12 months and less than 12 years with eczema, excluding inactive or very mild eczema (5 or less on Nottingham Eczema Severity Scale).Interventions: Children will be randomised to either bath emollients plus standard eczema care or standard eczema care only.Outcome measures: Primary outcome is long-term eczema severity, measured by the Patient-Oriented Eczema Measure (POEM) repeated weekly for 16 weeks. Secondary outcomes include: number of eczema exacerbations resulting in healthcare consultations over 1 year; eczema severity over 1 year; disease-specific and generic quality of life; medication use and healthcare resource use; cost-effectiveness. Aiming to detect a mean difference between groups of 2.0 (SD 7.0) in weekly POEM scores over 16 weeks (significance 0.05, power 0.9), allowing for 20% loss to follow-up, gives a total sample size of 423 children. We will use repeated measures analysis of covariance, or a mixed model, to analyse weekly POEM scores. We will control for possible confounders, including baseline eczema severity and child's age. Cost-effectiveness analysis will be carried out from a National Health Service (NHS) perspective.Ethics and disseminationThis protocol was approved by Newcastle and North Tyneside 1 NRES committee 14/NE/0098. Follow-up will be completed in 2017. Findings will be disseminated to participants and carers, the public, dermatology and primary care journals, guideline developers and decision-makers.Trial registration numberISRCTN84102309.
Achilles tendinopathy—do plantaris tendon removal and Achilles tendon scraping improve tendon structure? A prospective study using ultrasound tissue characterisation
Authors: Masci Lorenzo , Spang Christoph , van Schie Hans T M , Alfredson Håkan 
Published: November 2015

ObjectivesThe plantaris tendon has recently been described as a possible important factor in midportion Achilles tendinopathy. Ultrasound tissue characterisation (UTC) is a method to study tendon structure (matrix integrity). The effect of plantaris tendon removal on Achilles tendon structure was studied using UTC.Design and settingProspective case series study at one centre.ParticipantsNine tendons in eight physically active and healthy patients (mean age 39 years) with chronic painful midportion Achilles tendinopathy were included. Preoperative two-dimensional ultrasound and UTC showed midportion Achilles tendinopathy (tendinosis) with medial tendon changes and suspected plantaris tendon involvement. Patients with previous operations to the Achilles tendon were excluded.InterventionsOperative treatment consisted of excision of the plantaris tendon and scraping of the ventromedial surface of the Achilles tendon under a local anaesthetic.Primary and secondary outcome measuresUTC examination and clinical scoring with the VISA-A questionnaire were performed preoperatively and 6 months postoperatively.ResultsAt 6 months follow-up, UTC demonstrated a statistically significant (t=5.40, p<0.001) increase in the mean organised matrix (echo-type I+II) and a decrease in the mean disorganised matrix (echo-type III+IV). Seven out of eight patients were satisfied, and the VISA-A score had increased significantly (p<0.001) from 56.8 (range 34–73) preoperatively to 93.3 (range 87–100) postoperatively.ConclusionsExcision of the plantaris tendon and scraping of the ventromedial Achilles tendon in chronic midportion tendinopathy seem to have the potential to improve tendon structure and reduce tendon pain. Studies on a larger group of patients and with a longer follow-up period are needed.