bluuebunny/crossref_metadata_2025_split huggingface dataset:
An
In Vitro
Deletion in
ribE
Encoding Lumazine Synthase Contributes to Nitrofurantoin Resistance in Escherichia coli
Authors: Vervoort Jascha , Xavier Basil Britto , Stewardson Andrew , Coenen Samuel , Godycki-Cwirko Maciek , Adriaenssens Niels , Kowalczyk Anna , Lammens Christine , Harbarth Stephan , Goossens Herman , Malhotra-Kumar Surbhi 
Published: September 2014

ABSTRACT

Nitrofurantoin has been used for decades for the treatment of urinary tract infections (UTIs), but clinically significant resistance in
Escherichia coli
is uncommon. Nitrofurantoin concentrations in the gastrointestinal tract tend to be low, which might facilitate selection of nitrofurantoin-resistant (NIT-R) strains in the gut flora. We subjected two nitrofurantoin-susceptible intestinal
E. coli
strains (ST540-p and ST2747-p) to increasing nitrofurantoin concentrations under aerobic and anaerobic conditions. Whole-genome sequencing was performed for both susceptible isolates and selected mutants that exhibited the highest nitrofurantoin resistance levels aerobically (ST540-a and ST2747-a) and anaerobically (ST540-an and ST2747-an). ST540-a/ST540-an and ST2747-a (aerobic MICs of >64 μg/ml) harbored mutations in the known nitrofurantoin resistance determinants
nfsA
and/or
nfsB
, which encode oxygen-insensitive nitroreductases. ST2747-an showed reduced nitrofurantoin susceptibility (aerobic MIC of 32 μg/ml) and exhibited remarkable growth deficits but did not harbor
nfsA/nfsB
mutations. We identified a 12-nucleotide deletion in
ribE
, encoding lumazine synthase, an essential enzyme involved in the biosynthesis of flavin mononucleotide (FMN), which is an important cofactor for NfsA and NfsB. Complementing ST2747-an with a functional wild-type lumazine synthase restored nitrofurantoin susceptibility. Six NIT-R
E. coli
isolates (NRCI-1 to NRCI-6) from stools of UTI patients treated with nitrofurantoin, cefuroxime, or a fluoroquinolone harbored mutations in
nfsA
and/or
nfsB
but not
ribE
. Sequencing of the
ribE
gene in six intestinal and three urinary
E. coli
strains showing reduced nitrofurantoin susceptibility (MICs of 16 to 48 μg/ml) also did not identify any relevant mutations. NRCI-1, NRCI-2, and NRCI-5 exhibited up to 4-fold higher anaerobic MICs, compared to the mutants generated
in vitro
, presumably because of additional mutations in oxygen-sensitive nitroreductases.
The Small RNA RyhB Contributes to Siderophore Production and Virulence of Uropathogenic Escherichia coli
Authors: Porcheron Gaëlle , Habib Rima , Houle Sébastien , Caza Mélissa , Lépine François , Daigle France , Massé Eric , Dozois Charles M. 
Published: September 2014

ABSTRACT

In
Escherichia coli
, the small regulatory noncoding RNA (sRNA) RyhB and the global ferric uptake regulator (Fur) mediate iron acquisition and storage control. Iron is both essential and potentially toxic for most living organisms, making the precise maintenance of iron homeostasis necessary for survival. While the roles of these regulators in iron homeostasis have been well studied in a nonpathogenic
E. coli
strain, their impact on the production of virulence-associated factors is still unknown for a pathogenic
E. coli
strain. We thus investigated the roles of RyhB and Fur in iron homeostasis and virulence of the uropathogenic
E. coli
(UPEC) strain CFT073. In a murine model of urinary tract infection (UTI), deletion of
fur
alone did not attenuate virulence, whereas a Δ
ryhB
mutant and a Δ
fur
Δ
ryhB
double mutant showed significantly reduced bladder colonization. The Δ
fur
mutant was more sensitive to oxidative stress and produced more of the siderophores enterobactin, salmochelins, and aerobactin than the wild-type strain. In contrast, while RyhB was not implicated in oxidative stress resistance, the Δ
ryhB
mutant produced lower levels of siderophores. This decrease was correlated with the downregulation of
shiA
(encoding a transporter of shikimate, a precursor of enterobactin and salmochelin biosynthesis) and
iucD
(involved in aerobactin biosynthesis) in this mutant grown in minimal medium or in human urine.
iucD
was also downregulated in bladders infected with the Δ
ryhB
mutant compared to those infected with the wild-type strain. Our results thus demonstrate that the sRNA RyhB is involved in production of iron acquisition systems and colonization of the urinary tract by pathogenic
E. coli
.
FNR Regulates Expression of Important Virulence Factors Contributing to Pathogenicity of Uropathogenic Escherichia coli
Authors: Barbieri Nicolle L. , Nicholson Bryon , Hussein Ashraf , Cai Wentong , Wannemuehler Yvonne M. , Dell'Anna Giuseppe , Logue Catherine M. , Horn Fabiana , Nolan Lisa K. , Li Ganwu 
Published: September 2014

ABSTRACT

Uropathogenic
Escherichia coli
(UPEC) is responsible for the majority of urinary tract infections (UTIs), which are some of the world's most common bacterial infections of humans. Here, we examined the role of FNR (
f
umarate and
n
itrate
r
eduction), a well-known global regulator, in the pathogenesis of UPEC infections. We constructed an
fnr
deletion mutant of UPEC CFT073 and compared it to the wild type for changes in virulence, adherence, invasion, and expression of key virulence factors. Compared to the wild type, the
fnr
mutant was highly attenuated in the mouse model of human UTI and showed severe defects in adherence to and invasion of bladder and kidney epithelial cells. Our results showed that FNR regulates motility and multiple virulence factors, including expression of type I and P fimbriae, modulation of hemolysin expression, and expression of a novel pathogenicity island involved in α-ketoglutarate metabolism under anaerobic conditions. Our results demonstrate that FNR is a key global regulator of UPEC virulence and controls expression of important virulence factors that contribute to UPEC pathogenicity.
Investigation of the Essentiality of Glutamate Racemase in Mycobacterium smegmatis
Authors: Li Yang , Mortuza Roman , Milligan Daniel L. , Tran Sieu L. , Strych Ulrich , Cook Gregory M. , Krause Kurt L. 
Published: September 2014

ABSTRACTThe mycobacterial cell wall frequently has been used as a target for drug development, andd-glutamate, synthesized by glutamate racemase (MurI), is an important component of peptidoglycan. While the essentiality of themurIgene has been shown in several bacterial species, includingEscherichia coli,Bacillus anthracis, andStreptococcus pneumoniae, studies in mycobacteria have not yet provided definitive results. This study aimed to determine whethermurIis indeed essential and can serve as a possible target for structure-aided drug design. We have achieved this goal by creating a ΔmurIstrain ofMycobacterium smegmatis, a close relative ofMycobacterium tuberculosis. The deletion of themurIgene inM. smegmatiscould be achieved only in minimal medium supplemented withd-glutamate, demonstrating that MurI is essential for growth and that glutamate racemase is the only source ofd-glutamate for peptidoglycan synthesis inM. smegmatis.
The Cpx Envelope Stress Response Regulates and Is Regulated by Small Noncoding RNAs
Authors: Vogt Stefanie L. , Evans Alex D. , Guest Randi L. , Raivio Tracy L. 
Published: September 2014

ABSTRACT

The
Escherichia coli
genome encodes approximately 30 two-component systems that are required for sensing and responding to a variety of environmental and physiological cues. Recent studies have revealed numerous regulatory connections between two-component systems and small noncoding RNAs (sRNAs), which posttranscriptionally regulate gene expression by base pairing with target mRNAs. In this study, we investigated the role of sRNAs in the CpxAR two-component system, which detects and mediates an adaptive response to potentially lethal protein misfolding in the Gram-negative bacterial envelope. Here, we showed for the first time that sRNAs are members of the Cpx regulon. We found that CpxR binds to the promoter regions and regulates expression of two sRNA genes,
cyaR
and
rprA
. We also investigated the roles that these sRNAs play in the Cpx response. Cpx repression of
cyaR
expression creates a feed-forward loop, in which CpxAR increases expression of the inner membrane protein YqaE both directly at the transcriptional level and indirectly at the translational level. Moreover, we found that RprA exerts negative feedback on the Cpx response, reducing Cpx activity in a manner that is dependent on the response regulator CpxR but independent of all of RprA's previously described targets. sRNAs therefore permit the fine-tuning of Cpx pathway activity and its regulation of target genes, which could assist bacterial survival in the face of envelope stress.
Characterization of Biochemical Properties of Bacillus subtilis RecQ Helicase
Authors: Qin Wei , Liu Na-Nv , Wang Lijun , Zhou Min , Ren Hua , Bugnard Elisabeth , Liu Jie-Lin , Zhang Lin-Hu , Vendôme Jeremie , Hu Jin-Shan , Xi Xu Guang 
Published: September 2014

ABSTRACT

RecQ family helicases function as safeguards of the genome. Unlike
Escherichia coli
, the Gram-positive
Bacillus subtilis
bacterium possesses two RecQ-like homologues, RecQ[Bs] and RecS, which are required for the repair of DNA double-strand breaks. RecQ[Bs] also binds to the forked DNA to ensure a smooth progression of the cell cycle. Here we present the first biochemical analysis of recombinant RecQ[Bs]. RecQ[Bs] binds weakly to single-stranded DNA (ssDNA) and blunt-ended double-stranded DNA (dsDNA) but strongly to forked dsDNA. The protein exhibits a DNA-stimulated ATPase activity and ATP- and Mg
2+
-dependent DNA helicase activity with a 3′→5′ polarity. Molecular modeling shows that RecQ[Bs] shares high sequence and structure similarity with
E. coli
RecQ. Surprisingly, RecQ[Bs] resembles the truncated
Saccharomyces cerevisiae
Sgs1 and human RecQ helicases more than RecQ[Ec] with regard to its enzymatic activities. Specifically, RecQ[Bs] unwinds forked dsDNA and DNA duplexes with a 3′-overhang but is inactive on blunt-ended dsDNA and 5′-overhung duplexes. Interestingly, RecQ[Bs] unwinds blunt-ended DNA with structural features, including nicks, gaps, 5′-flaps, Kappa joints, synthetic replication forks, and Holliday junctions. We discuss these findings in the context of RecQ[Bs]'s possible functions in preserving genomic stability.
Physical impairments and activity limitations in people with femoroacetabular impingement: a systematic review
Authors: Diamond Laura E , Dobson Fiona L , Bennell Kim L , Wrigley Tim V , Hodges Paul W , Hinman Rana S 
Published: September 2014

BackgroundFemoroacetabular impingement (FAI) is a morphological hip condition that can cause hip and/or groin pain in younger active adults. Understanding the nature of physical impairments and activity limitations associated with symptomatic FAI is important to evaluate outcomes and guide development of rehabilitation strategies. The purpose of this systematic review was to establish: (1) whether people with symptomatic FAI demonstrate physical impairments and/or activity limitations compared with people without FAI; and (2) whether treatment affects these parameters.MethodsFour databases (Pubmed, CINAHL, SportDISCUS and Cochrane Library) were searched until the 21 June 2013. Studies evaluated measures of physical impairment and/or activity limitations in people with symptomatic FAI and included either: (1) a comparison control group; or (2) a pretreatment and post-treatment comparison. Methodological quality was assessed using the Newcastle-Ottawa Scale.Results16 studies were included. The most commonly reported physical impairment was decreased range of motion (ROM) into directions of hip joint impingement. Other impairments included altered sagittal and frontal plane hip ROM during gait, altered sagittal plane hip ROM during stair climbing, and decreased hip adductor and flexor muscle strength. Effects of surgery on physical impairments are inconsistent but suggest improved hip ROM during gait, but not during stair climbing. Squatting depth improves following surgical intervention for symptomatic FAI.ConclusionsPeople with symptomatic FAI demonstrate physical impairments and activity limitations. Surgical intervention may restore some deficiencies, but not all. Further studies of physical impairment and activity limitation are needed to evaluate outcomes from surgical and conservative interventions and to inform rehabilitation programmes.
Effectiveness of customised foot orthoses for Achilles tendinopathy: a randomised controlled trial
Authors: Munteanu Shannon E , Scott Lisa A , Bonanno Daniel R , Landorf Karl B , Pizzari Tania , Cook Jill L , Menz Hylton B 
Published: September 2014

AimTo evaluate the effectiveness of customised foot orthoses in chronic mid-portion Achilles tendinopathy.MethodsThis was a participant-blinded, parallel-group randomised controlled trial at a single centre (La Trobe University, Melbourne, Australia). One hundred and forty participants aged 18–55 years with mid-portion Achilles tendinopathy were randomised to receive eccentric calf muscle exercises with either customised foot orthoses (intervention group) or sham foot orthoses (control group). Allocation to intervention was concealed. The Victorian Institute of Sports Assessment-Achilles (VISA-A) questionnaire was completed at baseline, then at 1, 3, 6 and 12 months, with 3 months being the primary end point. Differences between groups were analysed using intention to treat with analysis of covariance.ResultsAfter randomisation into the customised foot orthoses group (n=67) or sham foot orthoses group (n=73), there was 70.7% follow-up of participants at 3 months. There were no significant differences between groups at any time point. At 3 months, the mean (SD) VISA-A score was 82.1 (16.3) and 79.2 (20.0) points for the customised and sham foot orthosis groups, respectively (adjusted mean difference (95% CI)=2.6 (−2.9 to 8.0), p=0.353). There were no clinically meaningful differences between groups in any of the secondary outcome measures.ConclusionsCustomised foot orthoses, prescribed according to the protocol in this study, are no more effective than sham foot orthoses for reducing symptoms and improving function in people with mid-portion Achilles tendinopathy undergoing an eccentric calf muscle exercise programme.Trial Registration NumberAustralian New Zealand Clinical Trials Registry: number ACTRN12609000829213.
Alcohol and drug use among adolescents: and the co-occurrence of mental health problems. Ung@hordaland, a population-based study
Authors: Skogen Jens Christoffer , Sivertsen Børge , Lundervold Astri J , Stormark Kjell Morten , Jakobsen Reidar , Hysing Mari 
Published: September 2014

ObjectivesThe use of alcohol and drugs is prevalent among adolescents, but too little is known about the association between debut of alcohol and drug use, problematic use and concurrent mental health. The aim of the study was to investigate the cross-sectional association between debut of any alcohol or drug use and alcohol-related and drug-related problems and mental health. We also wanted to examine potential interactions between gender and age, and alcohol-related and drug-related variables.DesignCross-sectional study.SettingPopulation-based sample of Norwegian adolescents.ParticipantsData stem from the large population-based ung@hordaland study (N=9203), where all adolescents aged 17–19 years living in Hordaland county (Norway) were invited to participate. The main independent variables were debut of alcohol and drug use, alcohol consumption and the presence of alcohol and drug problems as measured by CRAFFT.OutcomesThe dependent variables were self-reported symptoms of anxiety, depression, inattention and hyperactivity. Statistical analyses included logistic regression models.ResultsDebut of alcohol and drug use were associated with symptoms of depression, inattention and hyperactivity (crude ORs 1.69–2.38, p<0.001), while only debut of drug use was associated with increased symptoms of anxiety (OR=1.33, CI 95% 1.05 to 1.68, p=0.017). Alcohol-related and drug-related problems as measured by CRAFFT were associated with all mental health problems (crude ORs 1.68–3.24, p<0.001). There was little evidence of any substantial age or gender confounding on the estimated associations between alcohol-related and drug-related measures and mental health problems.ConclusionsEarly debut of alcohol and drug use and drug problems is consistently associated with more symptoms of mental health problems, indicating that these factors are an important general indicator of mental health in adolescence.
Community Based HIV Prevention Intervention in Developing Countries: A Systematic Review
Authors: Ibrahim Sarah , Sidani Souraya 
Published: September 2014

Aim. To describe the features and examine effects of community based HIV prevention interventions implemented in developing countries on HIV-related knowledge and self-reported risk behavior. Background. The HIV epidemic has a significant impact on developing countries, increasing the prevalence of HIV among young persons. Community-based HIV prevention interventions have been designed to improve HIV-related knowledge and decrease engagement in risk behavior. Variations in the design and implementation of these interventions have been reported, which may influence their effectiveness. Design. Systematic review. Method. Data were extracted on the characteristics of the study and interventions and effects of the interventions on knowledge and self-report of risk behavior. Results. In total, 10 studies were included in the review. Overall, the results showed variability in theoretical underpinning, dose, and mode of delivery of the interventions. Multicomponent interventions that used mixed teaching methods produced beneficial effects on knowledge and self-reported risk behavior. Conclusion. Examining the characteristics of HIV-prevention interventions provides direction for researchers in developing efficient interventions to improve knowledge and	reduce engagement in self-reported risk behavior and, in turn, decrease transmission of HIV.
Assessment of the Mandibular Incisive Canal by Panoramic Radiograph and Cone-Beam Computed Tomography
Authors: Raitz Ricardo , Shimura Elisabeth , Chilvarquer Israel , Fenyo-Pereira Marlene 
Published: September 2014

Objectives.The region between mental foramens is considered as a zone of choice for implants. However, complications may arise due to an extension anterior to the mental foramen that forms the mandible incisive canal [MIC]. Our goal is to evaluate identification of MIC by both panoramic radiograph [PAN] and cone-beam computed tomography [CBCT].Methods.150 cases with bilateral MIC were analyzed. Images of a radiolucent canal, within the trabecular bone, surrounded by a radiopaque cortical bone representing the canal walls, and extending to the anterior portion beyond the mental foramen, were considered by two independent radiologists as being images of MIC. PAN and CBCT of these cases were evaluated by 2 other radiologists at different times. Agreement between results of examination methods was assessed by the Kappa coefficient. The interexaminer and intramethod rates for detection of MIC were analyzed by the McNemar test. Gender, mandible side, examiner, and type of method were analyzed by the generalized estimating equations [GEE] model.Results.significant difference between examiners [PAN: P=0.146; CBCT:P=0.749] was not observed. Analysis by GEE model showed no significant difference between genders[P=0.411]and examiners[P=0.183]. However, significant difference was observed for identification in both mandible right side[P=0.001], where the identification frequency was higher, and CBCT method[P<0.001].Conclusions.PAN was not shown to be a safe examination to identify MIC. CBCT should always be used in preoperative planning and to reduce the number of complications in implant surgeries.
Honokiol Inhibits Lung Tumorigenesis through Inhibition of Mitochondrial Function
Authors: Pan Jing , Zhang Qi , Liu Qian , Komas Steven M. , Kalyanaraman Balaraman , Lubet Ronald A. , Wang Yian , You Ming 
Published: September 2014

Abstract
Honokiol is an important bioactive compound found in the bark of Magnolia tree. It is a nonadipogenic PPARγ agonist and capable of inhibiting the growth of a variety of tumor types both in vitro and in xenograft models. However, to fully appreciate the potential chemopreventive activity of honokiol, a less artificial model system is required. To that end, this study examined the chemopreventive efficacy of honokiol in an initiation model of lung squamous cell carcinoma (SCC). This model system uses the carcinogen N-nitroso-trischloroethylurea (NTCU), which is applied topically, reliably triggering the development of SCC within 24 to 26 weeks. Administration of honokiol significantly reduced the percentage of bronchial that exhibit abnormal lung SCC histology from 24.4% bronchial in control to 11.0% bronchial in honokiol-treated group (P = 0.01) while protecting normal bronchial histology (present in 20.5% of bronchial in control group and 38.5% of bronchial in honokiol-treated group. P = 0.004). P63 staining at the SCC site confirmed the lung SCCs phenotype. In vitro studies revealed that honokiol inhibited lung SCC cells proliferation, arrested cells at the G1–S cell-cycle checkpoint, while also leading to increased apoptosis. Our study showed that interfering with mitochondrial respiration is a novel mechanism by which honokiol changed redox status in the mitochondria, triggered apoptosis, and finally leads to the inhibition of lung SCC. This novel mechanism of targeting mitochondrial suggests honokiol as a potential lung SCC chemopreventive agent. Cancer Prev Res; 7(11); 1149–59. ©2014 AACR.
Cancer Immunoprevention—The Next Frontier
Authors: Smit Marie-Anne D. , Jaffee Elizabeth M. , Lutz Eric R. 
Published: September 2014

Abstract
Cancer immunotherapy is a rapidly developing field, but limited in its success by a high tumor burden and immune tolerance. In contrast, immunoprevention has the potential to prevent cancer before the development of immune tolerance, and to prevent cancer recurrence in the setting of minimal residual disease. Although immunoprevention for viral-induced cancers has been successful in the setting of hepatitis B and human papillomavirus vaccination, primary prevention of nonviral-induced cancers is in its infancy. In contrast, prevention of cancer recurrence after adjuvant treatment (secondary prevention) is gaining steam. This review provides an overview of the scope of research in cancer immunoprevention over the last three years and directions for future research.
See all articles in this Cancer Prevention Research collection, “Cancer Immunoprevention Series.”
Cancer Prev Res; 7(11); 1072–80. ©2014 AACR.