bluuebunny/crossref_metadata_2025 huggingface dataset:
Transonic Blade to Blade Calculations in an Axial, Radial or Mixed Flow Cascade Equipped With Splitter Blades
Authors: Bertheau Fernand , Ribaud Yves , Millour Valérie
Published: April 2015

A general computer code for pseudo-unsteady Euler equations integration in turbomachinery cascades has been developed. A quasi-three-dimensional flow hypothesis is assumed and only blade to blade calculation is considered here.

Cascades may be axial, radial or mixed flow type. First the computerized quasi-orthogonal network is shown. This network takes into account splitters and is designed to reduce the computation time.

Then, the numerical method is described and the major difficulties of this problem, which are boundary conditions, leading edge and trailing edge treatments, are presented. Finally, examples of calculations on turbines and compressors are given with emphasis on graphic representation.
Development of a Gas Turbine Combustion System for Medium-BTU Fuel
Authors: Savelli J. F. , Touchton G. L.
Published: April 2015

The Cool Water Coal Gasification Project requires a gas turbine combustion system to burn a high hydrogen medium-Btu coal gas produced in an oxygen-blown gasifier. The gas turbine selected for this demonstration plant is a General Electric Company MS7001E unit. The plant is located in Daggett, California, a location requiring compliance with stringent environmental regulations; that is, oxides of nitrogen (NOx) at 63.5 kg/hr and carbon monoxide (CO) at 35.0 kg/hr in the machine exhaust.

The plant operating configuration requires fuel gas to be supplied at 330 °K and 477 °K with 20%/vol moisture blended. A combustion system was developed enabling the gas turbine to operate from full speed no load to full load on both fuel gas configurations. Distillate oil capability was also incorporated to facilitate safe machine startup and shutdown.

Emissions requirements for NOx were met with steam injection, “CO” by combustor design, and sulfur oxides are met by fuel gas cleanup.

A conventional combustion liner sleeve with a standard air admission schedule was used. A unique fuel nozzle, based upon past low-Btu fuel work, was designed incorporating the latest low erosion oil nozzle.

One combustor of the 10 fitted to an MS7001E was tested at full pressure and airflow. Test results indicate, as predicted analytically, that NOx prediction varies substantially between cold dry fuel gas and hot wet gas. NOx compliance was attainable with little degradation of other design considerations. Carbon monoxide emissions were well below the required limits.
Rolls-Royce Marine Spey: A Shortcut to Longevity
Authors: Harry N. J. F. V.
Published: April 2015

In common with all responsible equipment operators the Royal Navy continues to seek ways to reduce ownership costs. In the particular case of gas turbines, over the last few years, this has taken the form of investment to achieve improvements in fuel efficiency. This route now ceases to offer large scope for improvement. The Royal Navy has therefore carried out an Investment Appraisal into the likely cost benefits which would result from improved life and reliability. The result of this study was to demonstrate a net present value cost advantage from entering into a joint venture development programme with Rolls-Royce to uprate and improve the Marine Spey SMIA.
Plasma jet's shielding gas impact on bacterial inactivation
Authors: Jablonowski Helena , Hänsch Mareike A. Ch. , Dünnbier Mario , Wende Kristian , Hammer Malte U. , Weltmann Klaus-Dieter , Reuter Stephan , von Woedtke Thomas
Published: April 2015

One of the most desired aims in plasma medicine is to inactivate prokaryotic cells and leave eukaryotic cells unharmed or even stimulate proliferation to promote wound healing. The method of choice is to precisely control the plasma component composition. Here the authors investigate the inactivation of bacteria (Escherichia coli) by a plasma jet treatment. The reactive species composition created by the plasma in liquids is tuned by the use of a shielding gas device to achieve a reactive nitrogen species dominated condition or a reactive oxygen species dominated condition. A strong correlation between composition of the reactive components and the inactivation of the bacteria is observed. The authors compare the results to earlier investigations on eukaryotic cells and show that it is possible to find a plasma composition where bacterial inactivation is strongest and adverse effects on eukaryotic cells are minimized.
Regional radiation dose susceptibility within the parotid gland: Effects on salivary loss and recovery
Authors: Clark Haley , Hovan Allan , Moiseenko Vitali , Thomas Steven , Wu Jonn , Reinsberg Stefan
Published: April 2015

Purpose:

Xerostomia is one of the most likely late toxic effects of radiotherapy treatment in patients with head‐and‐neck cancers. Modern treatment techniques can incorporate knowledge of complication risk into treatment plans. To this end, the authors attempt to quantify the regional radiotherapy dose‐dependence of salivary output loss and recovery in a prospective study.

Methods:

Salivary output was collected from patients undergoing radiotherapy treatment for head‐and‐neck cancers at the BC Cancer Agency between February 2008 and May 2013. Regional dose‐dependence (i.e., dose susceptibility) of loss and recovery is quantified using nonparametric (Spearman's rank correlation coefficients, local linear regression) and parametric (least‐sum of squares, least‐median of squares) techniques.

Results:

Salivary flow recovery was seen in 79 of 102 patients considered (p < 0.0001, Wilcoxon sign rank test). Output loss was strongly correlated with left‐ and right parotid combined dose φ = min (DL,  45 Gy) + min (DR,  45 Gy), and can be accurately predicted. Median early loss (three months) was 72% of baseline, while median overall loss (1 yr) was 56% of baseline. Fitting an exponential model to whole parotid yields dose sensitivities A3m = 0.0604 Gy−1 and A1y = 0.0379 Gy−1. Recovery was not significantly associated with dose. Hints of lateral organ sub‐segment dose–response dimorphism were observed.

Conclusions:

Sub‐segmentation appears to predict neither loss nor recovery with any greater precision than whole parotid mean dose, though it is not any worse. Sparing the parotid to a combined dose φ of <50 Gy is recommended for a patient to keep ≈40% of baseline function and thus avoid severe xerostomia at 12 months post‐treatment. It seems unlikely that a population's mean recovery will exceed 20%–30% of baseline output at 1 yr after radiotherapy treatment using current (whole‐organ based) clinical guidelines.
Association Between Television Viewing and Physical Activity in 10-Year-Old Brazilian Children
Authors: Ferrari Gerson Luis de Moraes , Araujo Timoteo Leandro , Oliveira Luis , Matsudo Victor , Mire Emily , Barreira Tiago V. , Tudor-Locke Catrine , Katzmarzyk Peter T.
Published: April 2015

Background:

Studies have found an association between television (TV) viewing and physical activity levels. The purpose of this study was to examine the association between TV viewing and physical activity in 10-year-old Brazilian children.

Methods:

The sample consisted of 485 children. Self-reported TV viewing on weekdays and weekends was assessed by questionnaire. An Actigraph GT3X+ accelerometer was used to monitor the range of physical activity intensities (including moderate-to-vigorous physical activity; MVPA), sedentary behavior (SB) and steps/day over 7 days.

Results:

Daily MVPA was highest among children viewing TV <1 hour/day (69 min) compared with children viewing 1 to 2 hours/day (61 min), 3 to 4 hours/day (55 min) and ≥ 5 hours/day (59 min) on weekdays (P = .0015). Differences in MVPA were not observed across TV categories on weekends. The prevalence of reaching 60 min/day of MVPA and 12,000 steps/day on weekdays was significantly greater in children viewing ≤ 2 hours/day (51.7% and 23.5%, respectively) compared with those viewing > 2 hours/day (38.6%, P = .0058; and 15.1%, P = .0291, respectively). There was no difference in SB across TV viewing categories.

Conclusion:

Time spent in MVPA and the frequency of meeting MVPA guidelines were significantly higher among children viewing ≤ 2 hours/day of TV on weekdays compared with those viewing more.
Using Shared Treadmill Workstations to Promote Less Time Spent in Daily Low Intensity Physical Activities: A Pilot Study
Authors: Bouchard Danielle R. , Strachan Shaelyn , Johnson Leslie , Moola Fiona , Chitkara Radhika , McMillan Diana , Myrie Semone , Giesbrecht Gordon
Published: April 2015

Objective:

Our objective was to test the feasibility of sharing treadmill workstations among office workers to reduce time spent at low intensity and explore changes in health outcomes after a 3-month intervention.

Methods:

Twenty-two office workers were asked to walk 2 hours per shift on a shared treadmill workstation for 3 months. Physical activity levels (ie, low, light, moderate, and vigorous), health-related measures (eg, sleep, blood pressure), treadmill usage information, and questions regarding participants’ expectation and experiences were collected.

Results:

Physical activity time at low intensity during workdays was reduced by 20.1% (P = .007) in the 71% of participants completing the study. Participants were 70% confident that they would keep using the treadmill workstations. Interestingly, systolic blood pressure, diastolic blood pressure, and sleep quality scores were significantly improved (P < .05).

Conclusions:

The use of such equipment to replace a few hours of sitting is feasible and might offer important health benefits.
Gender Differences in C-Reactive Protein and Muscle Strengthening Activity
Authors: Richardson Michael R. , Johnson Tammie M. , Katzmarzyk Peter T. , Ford Earl S. , Boyer William R. , Churilla James R.
Published: April 2015

Background:

Few studies have examined the gender differences between C-reactive protein (CRP) and muscle strengthening activity (MSA).

Methods:

The sample (n = 7533) included U.S. adult (≥20 years of age).participants in the 1999–2004 National Health and Nutrition Examination Survey (NHANES). Created categories of MSA participation included no MSA (referent group), some MSA (≥1 to <2 days/week), and meeting the 2008 Department of Health and Human Services (DHHS) recommendation (≥2 days/week). The dependent variable was elevated CRP (>3 to 10 mg/L).

Results:

Analysis revealed significantly lower odds of having elevated CRP for women reporting some MSA (OR 0.64; 95% CI 0.44–0.93, P = .0191). Significantly lower odds of men having elevated CRP was observed in those reporting MSA volumes meeting the DHHS recommendation (OR 0.72; 95% CI 0.59–0.88, P = .0019). Following adjustment for waist circumference (WC) these odds remained significant in men but not women.

Conclusions:

These results suggest that WC may mediate the associations between MSA and CRP and this relationship may be stronger in women.
Physical Activity Enjoyment, Perceived Barriers, and Beliefs Among Adolescents With and Without Intellectual Disabilities
Authors: Stanish Heidi I. , Curtin Carol , Must Aviva , Phillips Sarah , Maslin Melissa , Bandini Linda G.
Published: April 2015

Background:

Youths with intellectual disabilities (ID) exhibit low levels of physical activity, but the underlying contributors to behavior are unclear. We compared physical activity enjoyment, perceived barriers, beliefs, and self-efficacy among adolescents with ID and typically developing (TD) adolescents.

Methods:

A questionnaire was administered to 38 adolescents with ID (mean age, 16.8 years) and 60 TD adolescents (mean age, 15.3 years). Of the original 33 questionnaire items, 23 met the test-retest reliability criteria and were included in the group comparisons.

Results:

Fewer adolescents with ID reported that they have someone with whom to do physical activity (64% vs 93%: P < .001), and a greater percentage of adolescents with ID perceived that physical activities were too hard to learn (41% vs 0%; P < .001). Fewer adolescents with ID believed that physical activity would be good for their health (92% vs 100%; P = .05). More adolescents with ID reported a dislike of individual physical activities (P = .02). A large percentage of adolescents with ID (84%) responded that they were good at doing physical activities, but the difference between groups was only of borderline significance (95% of TD adolescents, P = .06).

Conclusions:

Adolescents shared many of the same perceptions about physical activity, but some important differences between groups were identified.
PTEN inhibits PREX2-catalyzed activation of RAC1 to restrain tumor cell invasion
Authors: Mense Sarah M. , Barrows Douglas , Hodakoski Cindy , Steinbach Nicole , Schoenfeld David , Su William , Hopkins Benjamin D. , Su Tao , Fine Barry , Hibshoosh Hanina , Parsons Ramon
Published: April 2015

Cancer-associated mutations in PREX2 enable cells to overcome the tumor-suppressive effects of PTEN.
New players in Lou Gehrig's disease
Authors: Hurtley Stella M.
Published: April 2015

Analysis of the expressed genes of nearly 2900 patients with amyotrophic lateral sclerosis and about 6400 controls reveals a disease predisposition–associated gene.
Rice that tolerates a chill
Authors: Gough Nancy R.
Published: April 2015

Variation in a single amino acid in a transmembrane protein confers cold tolerance to rice.
Engineering as a new frontier for translational medicine
Authors: Chien Shu , Bashir Rashid , Nerem Robert M. , Pettigrew Roderic
Published: April 2015

The inclusion of engineering ideas and approaches makes medicine a quantitative and systems-based discipline that facilitates precision diagnostics and therapeutics improving health care delivery for all.
In Vitro
Activities of Amphotericin B, Terbinafine, and Azole Drugs against Clinical and Environmental Isolates of Aspergillus terreus Sensu Stricto
Authors: Fernández Mariana S. , Rojas Florencia D. , Cattana María E. , Sosa María de los Ángeles , Iovannitti Cristina A. , Lass-Flörl Cornelia , Giusiano Gustavo E.
Published: April 2015

The antifungal susceptibilities of 40 clinical and environmental isolates of
A. terreus sensu stricto
to amphotericin B, terbinafine, itraconazole, and voriconazole were determined in accordance with CLSI document M38-A2. All isolates had itraconazole and voriconazole MICs lower than epidemiologic cutoff values, and 5% of the isolates had amphotericin B MICs higher than epidemiologic cutoff values. Terbinafine showed the lowest MICs. No significant differences were found when MICs of clinical and environmental isolates were compared.
High Prevalence of Mupirocin Resistance in Staphylococcus aureus Isolates from a Pediatric Population
Authors: Antonov Nina K. , Garzon Maria C. , Morel Kimberly D. , Whittier Susan , Planet Paul J. , Lauren Christine T.
Published: April 2015

Topical mupirocin is used widely to treat skin and soft tissue infections and to eradicate nasal carriage of methicillin-resistant
Staphylococcus aureus
(MRSA). Few studies to date have characterized the rates of
S. aureus
mupirocin resistance in pediatric populations. We retrospectively studied 358 unique
S. aureus
isolates obtained from 249 children seen in a predominantly outpatient setting by the Division of Pediatric Dermatology at a major academic center in New York City between 1 May 2012 and 17 September 2013. Mupirocin resistance rates and the associated risk factors were determined using a logistic regression analysis. In our patient population, 19.3% of patients had mupirocin-resistant
S. aureus
isolates at the time of their first culture, and 22.1% of patients with
S. aureus
infection had a mupirocin-resistant isolate at some time during the study period. Overall, 31.3% of all
S. aureus
isolates collected during the study period were resistant to mupirocin. Prior mupirocin use was strongly correlated (odds ratio [OR] = 26.5;
P
= <0.001) with mupirocin resistance. Additional risk factors for mupirocin resistance included methicillin resistance, atopic dermatitis (AD), epidermolysis bullosa (EB), immunosuppression, and residence in northern Manhattan and the Bronx. Resistance to mupirocin is widespread in children with dermatologic complaints in the New York City area, and given the strong association with mupirocin exposure, it is likely that mupirocin use contributes to the increased resistance. Routine mupirocin testing may be important for MRSA decolonization strategies or the treatment of minor skin infections in children.
Population Pharmacokinetic Analysis for a Single 1,200-Milligram Dose of Oritavancin Using Data from Two Pivotal Phase 3 Clinical Trials
Authors: Rubino C. M. , Bhavnani S. M. , Moeck G. , Bellibas S. E. , Ambrose P. G.
Published: April 2015

Oritavancin is a lipoglycopeptide antibiotic with activity against Gram-positive bacteria. Here we describe oritavancin population pharmacokinetics and the impact of patient-specific covariates on drug exposure variability. Concentration-time data were analyzed from two phase 3 clinical trials, SOLO I and SOLO II, in which oritavancin was administered as a single 1,200-mg dose to patients with acute bacterial skin and skin structure infections. A total of 1,337 drug concentrations from 297 patients (90% of whom had 4 or 5 pharmacokinetic samples) were available for analysis. A previously derived population model based on data from 12 phase 1, 2, and 3 oritavancin studies was applied to the SOLO data set. Alterations to the structural model were made, as necessary, based on model fit. Analyses utilized Monte Carlo parametric expectation maximization (S-ADAPT 1.5.6). The previous population pharmacokinetic model fit the data well (
r
2
= 0.972), and population pharmacokinetic parameters were estimated with acceptable precision and lack of bias. Covariate evaluations revealed statistically significant relationships between central compartment volume and age and between clearance and height; however, these relationships did not indicate a clinically relevant impact on oritavancin exposure over the range of age and height observed in the SOLO studies. The mean (coefficient of variation [CV]) area under the plasma concentration-time curve from time zero to 72 h (AUC
0–72
) and maximum plasma concentration (
C
max
) were 1,530 (36.9%) μg · h/ml and 138 (23%) μg/ml, respectively. The mean (CV) half-life at alpha phase (
t
1/2α
),
t
1/2β
, and
t
1/2γ
were 2.29 (49.8%), 13.4 (10.5%), and 245 (14.9%) hours, respectively. These analyses are the first to describe oritavancin pharmacokinetics following a single 1,200-mg dose. Covariate analyses suggested that no dose adjustments are required for renal impairment (creatinine clearance, >29 ml/min), mild or moderate hepatic impairment, age, weight, gender, or diabetes status.
Sphingolipids Mediate Differential Echinocandin Susceptibility in Candida albicans and Aspergillus nidulans
Authors: Healey Kelley R. , Challa Krishna K. , Edlind Thomas D. , Katiyar Santosh K.
Published: April 2015

The cell wall synthesis-inhibiting echinocandins, including caspofungin and micafungin, play important roles in the treatment of candidiasis and aspergillosis. Previous studies revealed that, in the haploid yeast
Candida glabrata
, sphingolipid biosynthesis pathway mutations confer caspofungin reduced susceptibility (CRS) but micafungin increased susceptibility (MIS). Here, we describe one
Candida albicans
strain (of 10 tested) that similarly yields CRS-MIS mutants at relatively high frequency. Mutants demonstrated increased levels of long-chain bases (sphingolipid pathway intermediates) and, unique to this strain, loss of His104/Pro104 heterozygosity in the
TSC13
-encoded enoyl reductase. CRS-MIS was similarly observed in a
C. albicans
homozygous
fen1
Δ
fen12
Δ laboratory strain and in diverse wild-type strains following exogenous long-chain-base treatment. Analogous to these results, CRS-MIS was demonstrated in an
Aspergillus nidulans
basA
mutant encoding defective sphingolipid C
4
-hydroxylase and in its wild-type parent exposed to long-chain bases. Sphingolipids likely modulate echinocandin interaction with their Fks membrane target in all susceptible fungi, with potential implications for optimizing therapy with existing antifungals and the development of novel agents.
Efflux as a Glutaraldehyde Resistance Mechanism in Pseudomonas fluorescens and Pseudomonas aeruginosa Biofilms
Authors: Vikram Amit , Bomberger Jennifer M. , Bibby Kyle J.
Published: April 2015

A major challenge in microbial biofilm control is biocide resistance. Phenotypic adaptations and physical protective effects have been historically thought to be the primary mechanisms for glutaraldehyde resistance in bacterial biofilms. Recent studies indicate the presence of genetic mechanisms for glutaraldehyde resistance, but very little is known about the contributory genetic factors. Here, we demonstrate that efflux pumps contribute to glutaraldehyde resistance in
Pseudomonas fluorescens
and
Pseudomonas aeruginosa
biofilms. The RNA-seq data show that efflux pumps and phosphonate degradation, lipid biosynthesis, and polyamine biosynthesis metabolic pathways were induced upon glutaraldehyde exposure. Furthermore, chemical inhibition of efflux pumps potentiates glutaraldehyde activity, suggesting that efflux activity contributes to glutaraldehyde resistance. Additionally, induction of known modulators of biofilm formation, including phosphonate degradation, lipid biosynthesis, and polyamine biosynthesis, may contribute to biofilm resistance and resilience. Fundamental understanding of the genetic mechanism of biocide resistance is critical for the optimization of biocide use and development of novel disinfection strategies. Our results reveal genetic components involved in glutaraldehyde resistance and a potential strategy for improved control of biofilms.
Oral Tolerance Failure upon Neonatal Gut Colonization with Escherichia coli Producing the Genotoxin Colibactin
Authors: Secher Thomas , Payros Delphine , Brehin Camille , Boury Michele , Watrin Claude , Gillet Marion , Bernard-Cadenat Isabelle , Menard Sandrine , Theodorou Vassilia , Saoudi Abdelhadi , Olier Maiwenn , Oswald Eric
Published: April 2015

The intestinal barrier controls the balance between tolerance and immunity to luminal antigens. When this finely tuned equilibrium is deregulated, inflammatory disorders can occur. There is a concomitant increase, in urban populations of developed countries, of immune-mediated diseases along with a shift in
Escherichia coli
population from the declining phylogenetic group A to the newly dominant group B2, including commensal strains producing a genotoxin called colibactin that massively colonized the gut of neonates. Here, we showed that mother-to-offspring early gut colonization by colibactin-producing
E. coli
impairs intestinal permeability and enhances the transepithelial passage of luminal antigen, leading to an increased immune activation. Functionally, this was accompanied by a dramatic increase in local and systemic immune responses against a fed antigen, decreased regulatory T cell population, tolerogenic dendritic cells, and enhanced mucosal delayed-type hypersensitivity response. Conversely, the abolition of colibactin expression by mutagenesis abrogates the alteration of oral tolerance induced by neonatal colonization by
E. coli
. In conclusion, the vertical colonization by
E. coli
producing the genotoxin colibactin enhances intestinal translocation and subsequently alters oral tolerance. Thus, early colonization by
E. coli
from the newly dominant phylogenetic group B2, which produces colibactin, may represent a risk factor for the development of immune-mediated diseases.
Cytotoxic and Apoptotic Effects of Recombinant Subtilase Cytotoxin Variants of Shiga Toxin-Producing Escherichia coli
Authors: Funk J. , Biber N. , Schneider M. , Hauser E. , Enzenmüller S. , Förtsch C. , Barth H. , Schmidt H.
Published: April 2015

In this study, the cytotoxicity of the recently described subtilase variant SubAB
2-2
of Shiga toxin-producing
Escherichia coli
was determined and compared to the plasmid-encoded SubAB
1
and the chromosome-encoded SubAB
2-1
variant. The genes for the respective enzymatic active (A) subunits and binding (B) subunits of the subtilase toxins were amplified and cloned. The recombinant toxin subunits were expressed and purified. Their cytotoxicity on Vero cells was measured for the single A and B subunits, as well as for mixtures of both, to analyze whether hybrids with toxic activity can be identified. The results demonstrated that all three SubAB variants are toxic for Vero cells. However, the values for the 50% cytotoxic dose (CD
50
) differ for the individual variants. Highest cytotoxicity was shown for SubAB
1
. Moreover, hybrids of subunits from different subtilase toxins can be obtained which cause substantial cytotoxicity to Vero cells after mixing the A and B subunits prior to application to the cells, which is characteristic for binary toxins. Furthermore, higher concentrations of the enzymatic subunit SubA
1
exhibited cytotoxic effects in the absence of the respective B
1
subunit. A more detailed investigation in the human HeLa cell line revealed that SubA
1
alone induced apoptosis, while the B
1
subunit alone did not induce cell death.
Inhibition of Cell Differentiation in Bacillus subtilis by Pseudomonas protegens
Authors: Powers Matthew J. , Sanabria-Valentín Edgardo , Bowers Albert A. , Shank Elizabeth A.
Published: April 2015

Interspecies interactions have been described for numerous bacterial systems, leading to the identification of chemical compounds that impact bacterial physiology and differentiation for processes such as biofilm formation. Here, we identified soil microbes that inhibit biofilm formation and sporulation in the common soil bacteriumBacillus subtilis. We did so by creating a reporter strain that fluoresces when the transcription of a biofilm-specific gene is repressed. Using this reporter in a coculture screen, we identifiedPseudomonas putidaandPseudomonas protegensas bacteria that secrete compounds that inhibit biofilm gene expression inB. subtilis. The active compound produced byP. protegenswas identified as the antibiotic and antifungal molecule 2,4-diacetylphloroglucinol (DAPG). Colonies ofB. subtilisgrown adjacent to a DAPG-producingP. protegensstrain had altered colony morphologies relative toB. subtiliscolonies grown next to a DAPG-nullP. protegensstrain (phlDstrain). Using a subinhibitory concentration of purified DAPG in a pellicle assay, we saw that biofilm-specific gene transcription was delayed relative to transcription in untreated samples. These transcriptional changes also corresponded to phenotypic alterations: both biofilm biomass and spore formation were reduced inB. subtilisliquid cultures treated with subinhibitory concentrations of DAPG. Our results add DAPG to the growing list of antibiotics that impact bacterial development and physiology at subinhibitory concentrations. These findings also demonstrate the utility of using coculture as a means to uncover chemically mediated interspecies interactions between bacteria.

IMPORTANCEBiofilms are communities of bacteria adhered to surfaces by an extracellular matrix; such biofilms can have important effects in both clinical and agricultural settings. To identify chemical compounds that inhibited biofilm formation, we used a fluorescent reporter to screen for bacteria that inhibited biofilm gene expression inBacillus subtilis. We identifiedPseudomonas protegensas one such bacterium and found that the biofilm-inhibiting compound it produces was the antibiotic 2,4-diacetylphloroglucinol (DAPG). We showed that even at subinhibitory concentrations, DAPG inhibits biofilm formation and sporulation inB. subtilis. These findings have potential implications for understanding the interactions between these two microbes in the natural world and support the idea that many compounds considered antibiotics can impact bacterial development at subinhibitory concentrations.
Subinhibitory Antibiotic Therapy Alters Recurrent Urinary Tract Infection Pathogenesis through Modulation of Bacterial Virulence and Host Immunity
Authors: Goneau Lee W. , Hannan Thomas J. , MacPhee Roderick A. , Schwartz Drew J. , Macklaim Jean M. , Gloor Gregory B. , Razvi Hassan , Reid Gregor , Hultgren Scott J. , Burton Jeremy P.
Published: April 2015

The capacity of subinhibitory levels of antibiotics to modulate bacterial virulencein vitrohas recently been brought to light, raising concerns over the appropriateness of low-dose therapies, including antibiotic prophylaxis for recurrent urinary tract infection management. However, the mechanisms involved and their relevance in influencing pathogenesis have not been investigated. We characterized the ability of antibiotics to modulate virulence in the uropathogensStaphylococcus saprophyticusandEscherichia coli. Several antibiotics were able to induce the expression of adhesins critical to urothelial colonization, resulting in increased biofilm formation, colonization of murine bladders and kidneys, and promotion of intracellular niche formation. Mice receiving subinhibitory ciprofloxacin treatment were also more susceptible to severe infections and frequent recurrences. A ciprofloxacin prophylaxis model revealed this strategy to be ineffective in reducing recurrences and worsened infection by creating larger intracellular reservoirs at higher frequencies. Our study indicates that certain agents used for antibiotic prophylaxis have the potential to complicate infections.

IMPORTANCEAntibiotics are the mainstay treatment for bacterial infections; however, evidence is emerging that argues these agents may have off-target effects if sublethal concentrations are present. Most studies have focused on changes occurringin vitro, leaving questions regarding the clinical relevancein vivo. We utilized a murine urinary tract infection model to explore the potential impact of low-dose antibiotics on pathogenesis. Using this model, we showed that subinhibitory antibiotics prime uropathogens for adherence and invasion of murine urothelial tissues. These changes in initial colonization promoted the establishment of chronic infection. Furthermore, treatment of chronically infected mice with subtherapeutic ciprofloxacin served to exacerbate infection. A part of these changes was thought to be due to suppression of mucosal immunity, as demonstrated through reductions in cytokine secretion and migration of leukocytes into the urinary tract. This work identifies novel risk factors associated with antibiotic therapy when dosing strategies fall below subtherapeutic levels.
Structural and Mechanistic Roles of Novel Chemical Ligands on the SdiA Quorum-Sensing Transcription Regulator
Authors: Nguyen Y , Nguyen Nam X. , Rogers Jamie L. , Liao Jun , MacMillan John B. , Jiang Youxing , Sperandio Vanessa
Published: April 2015

Bacteria engage in chemical signaling, termed quorum sensing (QS), to mediate intercellular communication, mimicking multicellular organisms. The LuxR family of QS transcription factors regulates gene expression, coordinating population behavior by sensing endogenous acyl homoserine lactones (AHLs). However, some bacteria (such as
Escherichia coli
) do not produce AHLs. These LuxR orphans sense exogenous AHLs but also regulate transcription in the absence of AHLs. Importantly, this AHL-independent regulatory mechanism is still largely unknown. Here we present several structures of one such orphan LuxR-type protein, SdiA, from enterohemorrhagic
E. coli
(EHEC), in the presence and absence of AHL. SdiA is actually not in an apo state without AHL but is regulated by a previously unknown endogenous ligand, 1-octanoyl-
rac
-glycerol (OCL), which is ubiquitously found throughout the tree of life and serves as an energy source, signaling molecule, and substrate for membrane biogenesis. While exogenous AHL renders to SdiA higher stability and DNA binding affinity, OCL may function as a chemical chaperone placeholder that stabilizes SdiA, allowing for basal activity. Structural comparison between SdiA-AHL and SdiA-OCL complexes provides crucial mechanistic insights into the ligand regulation of AHL-dependent and -independent function of LuxR-type proteins. Importantly, in addition to its contribution to basic science, this work has implications for public health, inasmuch as the SdiA signaling system aids the deadly human pathogen EHEC to adapt to a commensal lifestyle in the gastrointestinal (GI) tract of cattle, its main reservoir. These studies open exciting and novel avenues to control shedding of this human pathogen in the environment.

IMPORTANCE
Quorum sensing refers to bacterial chemical signaling. The QS acyl homoserine lactone (AHL) signals are recognized by LuxR-type receptors that regulate gene transcription. However, some bacteria have orphan LuxR-type receptors and do not produce AHLs, sensing them from other bacteria. We solved three structures of the
E. coli
SdiA orphan, in the presence and absence of AHL. SdiA with no AHL is not in an apo state but is regulated by a previously unknown endogenous ligand, 1-octanoyl-
rac
-glycerol (OCL). OCL is ubiquitously found in prokaryotes and eukaryotes and is a phospholipid precursor for membrane biogenesis and a signaling molecule. While AHL renders to SdiA higher stability and DNA-binding affinity, OCL functions as a chemical chaperone placeholder, stabilizing SdiA and allowing for basal activity. Our studies provide crucial mechanistic insights into the ligand regulation of SdiA activity.
Virus-Induced Dormancy in the Archaeon Sulfolobus islandicus
Authors: Bautista Maria A. , Zhang Changyi , Whitaker Rachel J.
Published: April 2015

We investigated the interaction between Sulfolobus spindle-shaped virus (SSV9) and its native archaeal host
Sulfolobus islandicus
. We show that upon exposure to SSV9, S. islandicus strain RJW002 has a significant growth delay where the majority of cells are dormant (viable but not growing) for 24 to 48 hours postinfection (hpi) compared to the growth of controls without virus. We demonstrate that in this system, dormancy (i) is induced by both active and inactive virus particles at a low multiplicity of infection (MOI), (ii) is reversible in strains with active CRISPR-Cas immunity that prevents the establishment of productive infections, and (iii) results in dramatic and rapid host death if virus persists in the culture even at low levels. Our results add a new dimension to evolutionary models of virus-host interactions, showing that the mere presence of a virus induces host cell stasis and death independent of infection. This novel, highly sensitive, and risky bet-hedging antiviral response must be integrated into models of virus-host interactions in this system so that the true ecological impact of viruses can be predicted and understood.

IMPORTANCE
Viruses of microbes play key roles in microbial ecology; however, our understanding of viral impact on host physiology is based on a few model bacteria that represent a small fraction of the life history strategies employed by hosts or viruses across the three domains that encompass the microbial world. We have demonstrated that rare and even inactive viruses induce dormancy in the model archaeon S. islandicus. Similar virus-induced dormancy strategies in other microbial systems may help to explain several confounding observations in other systems, including the surprising abundance of dormant cell types found in many microbial environments, the difficulty of culturing microorganisms in the laboratory, and the paradoxical virus-to-host abundances that do not match model predictions. A more accurate grasp of virus-host interactions will expand our understanding of the impact of viruses in microbial ecology.
Cryptococcus neoformans Host Adaptation: Toward Biological Evidence of Dormancy
Authors: Alanio Alexandre , Vernel-Pauillac Frédérique , Sturny-Leclère Aude , Dromer Françoise
Published: April 2015

Cryptococcosis is an opportunistic infection due to the ubiquitous yeast
Cryptococcus neoformans
. This yeast interacts closely with innate immune cells, leading to various fates, including fungal persistence within cells, making possible the dissemination of the yeast cells with monocytes via a Trojan horse strategy. In humans, the natural history of the infection begins with primoinfection during childhood, which is followed by dormancy and, in some individuals, reactivation upon immunosuppression. To address the question of dormancy, we studied
C. neoformans
infection at the macrophage level (
in vitro
H99-macrophage interaction) and at the organ level in a murine model of cryptococcosis. We analyzed the diversity of yeast adaptation to the host by characterizing several
C. neoformans
populations with new assays based on flow cytometry (quantitative flow cytometry, multispectral imaging flow cytometry, sorting), microscopy (dynamic imaging), and gene expression analysis. On the basis of parameters of multiplication and stress response, various populations of yeast cells were observed over time
in vivo
and
in vitro
. Cell sorting allowed the identification of a subpopulation that was less prone to grow under standard conditions than the other populations, with growth enhanced by the addition of serum. Gene expression analysis revealed that this population had specific metabolic characteristics that could reflect dormancy. Our data suggest that dormant yeast cells could exist
in vitro
and
in vivo
.
C. neoformans
exhibits a huge plasticity and adaptation to hosts that deserves further study.
In vitro
generation of dormant cells is now the main challenge to overcome the limited number of yeast cells recovered in our models.

IMPORTANCE
Cryptococcus neoformans
is a sugar-coated unicellular fungus that interacts closely with various cells and organisms, including amoebas, nematodes, and immune cells of mammals. This yeast is able to proliferate and survive in the intracellular environment.
C. neoformans
causes cryptococcosis, and yeast dormancy in humans has been suggested on the basis of epidemiological evidence obtained years ago. By studying an
in vitro
model of yeast-macrophage interaction and murine models of cryptococcosis, we observed that yeast cells evolve in heterogeneous populations during infection on the basis of global metabolic activity. We compared the growth ability and gene expression of yeast cells belonging to various populations in those two models. We eventually found a population of yeast cells with low metabolism that fit some of the criteria for dormant cells. This paves the way for further characterization of dormancy in
C. neoformans
.
Child development assessment tools in low-income and middle-income countries: how can we use them more appropriately?
Authors: Sabanathan Saraswathy , Wills Bridget , Gladstone Melissa
Published: April 2015

Global emphasis has shifted beyond reducing child survival rates to improving health and developmental trajectories in childhood. Optimum early childhood experience is believed to allow children to benefit fully from educational opportunities resulting in improved human capital. Investment in early childhood initiatives in low-income and middle-income countries (LMICs) is increasing. These initiatives use early childhood developmental assessment tools (CDATs) as outcome measures. CDATs are also key measures in the evaluation of programmatic health initiatives in LMICs, influencing public health policy. Interpretation of CDAT outcomes requires understanding of their structure and psychometric properties. This article reviews the structure and main methods of CDAT development with specific considerations when applied in LMICs.
Residual vasomotor activity assessed by heart rate variability in a brain-dead case
Authors: Machado Calixto , Estevez Mario , Perez-Nellar Jesus , Schiavi Adam
Published: April 2015

A patient assessed by heart rate variability (HRV) methodology, beginning just after the completion of brain death (BD) diagnosis, showed remaining very low frequency (VLF) waves for approximately 10 min. A time-varying spectral analysis showed that during the first 550 s, a significant power spectral density remained in the high-frequency (HF), low-frequency (LF) and VLF bands. From 550 to 675 s, the HF oscillations totally vanished, and a marked progressive decay of the LF and VLF power density occurred. After 700 s the VLF undulations stopped and remaining small amplitude oscillations at 0.2 Hz coincided with the ventilator frequency. The VLF oscillations recorded in our case might be related to residual sympathetic vasomotor activity that progressively disappeared due to the extension of necrosis affecting the nervous centres of the lower part of the medulla and the first 2–3 cervical spine segments.
Burning mouth syndrome due to herpes simplex virus type 1
Authors: Nagel Maria A , Choe Alexander , Traktinskiy Igor , Gilden Don
Published: April 2015

Burning mouth syndrome is characterised by chronic orofacial burning pain. No dental or medical cause has been found. We present a case of burning mouth syndrome of 6 months duration in a healthy 65-year-old woman, which was associated with high copy numbers of herpes simplex virus type 1 (HSV-1) DNA in the saliva. Her pain resolved completely after antiviral treatment with a corresponding absence of salivary HSV-1 DNA 4 weeks and 6 months later.
Exercise-associated DNA methylation change in skeletal muscle and the importance of imprinted genes: a bioinformatics meta-analysis
Authors: Brown William M
Published: April 2015

Background

Epigenetics is the study of processes—beyond DNA sequence alteration—producing heritable characteristics. For example, DNA methylation modifies gene expression without altering the nucleotide sequence. A well-studied DNA methylation-based phenomenon is genomic imprinting (ie, genotype-independent parent-of-origin effects).

Objective

We aimed to elucidate: (1) the effect of exercise on DNA methylation and (2) the role of imprinted genes in skeletal muscle gene networks (ie, gene group functional profiling analyses).

Design

Gene ontology (ie, gene product elucidation)/meta-analysis.

Data sources

26 skeletal muscle and 86 imprinted genes were subjected to g:Profiler ontology analysis. Meta-analysis assessed exercise-associated DNA methylation change.

Data extraction

g:Profiler found four muscle gene networks with imprinted loci. Meta-analysis identified 16 articles (387 genes/1580 individuals) associated with exercise. Age, method, sample size, sex and tissue variation could elevate effect size bias.

Data synthesis

Only skeletal muscle gene networks including imprinted genes were reported. Exercise-associated effect sizes were calculated by gene. Age, method, sample size, sex and tissue variation were moderators.

Results

Six imprinted loci (RB1,MEG3,UBE3A,PLAGL1,SGCE,INS) were important for muscle gene networks, while meta-analysis uncovered five exercise-associated imprinted loci (KCNQ1,MEG3,GRB10,L3MBTL1,PLAGL1). DNA methylation decreased with exercise (60% of loci). Exercise-associated DNA methylation change was stronger among older people (ie, age accounted for 30% of the variation). Among older people, genes exhibiting DNA methylation decreases were part of a microRNA-regulated gene network functioning to suppress cancer.

Conclusions

Imprinted genes were identified in skeletal muscle gene networks and exercise-associated DNA methylation change. Exercise-associated DNA methylation modification could rewind the ‘epigenetic clock’ as we age.

Trial registration number

CRD42014009800.
An examination of concussion education programmes: a scoping review methodology
Authors: Caron Jeffrey G , Bloom Gordon A , Falcão William R , Sweet Shane N
Published: April 2015

Objectives

The primary purpose was to review the literature on concussion education programmes. The secondary purpose was to inform knowledge translation strategies for concussion researchers and practitioners.

Design

Research on concussion education programmes is relatively new. As a result, the current study implemented a scoping review methodology, which is a type of literary search used to provide a preliminary assessment of the size and scope of a body of literature, as well as identify strengths, weaknesses and gaps in the research.

Methods

A five-stage process for conducting a scoping review was followed for this study: (a) identifying the research questions, (b) identifying relevant studies, (c) identifying the study selection criteria, (d) charting the data and (e) reporting the results.

Results

Concussion education programmes have been developed and implemented with populations ranging in age from 9 to 49 years and have used interactive oral presentations, educational videos and computer-based learning programmes. Although the content of these programmes varied, the topics generally addressed salient aspects of concussion injury and recovery. Quantitative instruments have been the preferred methods for assessment.

Conclusions

Education programmes aimed at improving participants’ long-term concussion knowledge, behaviours and attitudes of concussions are needed. Researchers must consider using a knowledge translation framework to enhance concussion education programmes. The application of such a framework can lead to novel and interesting ways of disseminating information about concussive injury and recovery.
Plasma carnosine, but not muscle carnosine, attenuates high-fat diet-induced metabolic stress
Authors: Stegen Sanne , Stegen Bram , Aldini Giancarlo , Altomare Alessandra , Cannizzaro Luca , Orioli Marica , Gerlo Sarah , Deldicque Louise , Ramaekers Monique , Hespel Peter , Derave Wim
Published: April 2015

There is growing in vivo evidence that the dipeptide carnosine has protective effects in metabolic diseases. A critical unanswered question is whether its site of action is tissues or plasma. This was investigated using oral carnosine versus β-alanine supplementation in a high-fat diet rat model. Thirty-six male Sprague–Dawley rats received a control diet (CON), a high-fat diet (HF; 60% of energy from fat), the HF diet with 1.8% carnosine (HFcar), or the HF diet with 1% β-alanine (HFba), as β-alanine can increase muscle carnosine without increasing plasma carnosine. Insulin sensitivity, inflammatory signaling, and lipoxidative stress were determined in skeletal muscle and blood. In a pilot study, urine was collected. The 3 HF groups were significantly heavier than the CON group. Muscle carnosine concentrations increased equally in the HFcar and HFba groups, while elevated plasma carnosine levels and carnosine–4-hydroxy-2-nonenal adducts were detected only in the HFcar group. Elevated plasma and urine Nε-(carboxymethyl)lysine in HF rats was reduced by ∼50% in the HFcar group but not in the HFba group. Likewise, inducible nitric oxide synthase mRNA was decreased by 47% (p < 0.05) in the HFcar group, but not in the HFba group, compared with HF rats. We conclude that plasma carnosine, but not muscle carnosine, is involved in preventing early-stage lipoxidation in the circulation and inflammatory signaling in the muscle of rats.
Topological invariant quintessence
Authors: De Laurentis Mariafelicia
Published: April 2015

The issues of quintessence and cosmic acceleration can be discussed in the framework of [Formula: see text] theories of gravity where R is the Ricci curvature scalar and [Formula: see text] is the Gauss–Bonnet topological invariant. It is possible to show that such an approach exhausts all the curvature content related to the Riemann tensor giving rise to a fully geometric approach to dark energy.
Renormalization group theory, the epsilon expansion and Ken Wilson as I knew him
Authors: Fisher Michael E.
Published: April 2015

The tasks posed for renormalization group theory (RGT) within statistical physics by critical phenomena theory in the 1960's are set out briefly in contradistinction to quantum field theory (QFT), which was the origin for Ken Wilson's concerns. Kadanoff's 1966 block spin scaling picture and its difficulties are presented; Wilson's early vision of flows is described from the author's perspective. How Wilson's subsequent breakthrough ideas, published in 1971, led to the epsilon expansion and the resulting clarity is related. Concluding sections complete the general picture of flows in a space of Hamiltonians, universality and scaling. The article represents a 40% condensation (but with added items) of an earlier account: Rev. Mod. Phys.70, 653–681 (1998).