bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential Activation of Staphylococcus aureus Heme Detoxification Machinery by Heme Analogues
Authors: Wakeman Catherine A. , Stauff Devin L. , Zhang Yaofang , Skaar Eric P. 
Published: January 2014

ABSTRACT

The reactive nature of heme enables its use as an enzymatic cofactor while rendering excess heme toxic. The importance of heme detoxification machinery is highlighted by the presence of various types of these homeostatic systems in Gram-positive and Gram-negative microorganisms. A number of pathogens possess orthologs of the HssRS/HrtAB heme detoxification system, underscoring a potential role this system plays in the survival of bacteria in heme-rich environments such as the vertebrate host. In this work, we sought to determine the role of this system in protection against metalloporphyrin heme analogues identified by previous studies as antimicrobial agents. Our findings demonstrate that only toxic metalloporphyrins maximally activate expression of the
Staphylococcus aureus
heme detoxification system, suggesting that the sensing mechanism of HssRS might require a component of the associated toxicity rather than or in addition to the metalloporphyrin itself. We further establish that only a subset of toxic metalloporphyrins elicit the oxidative damage previously shown to be a significant component of heme toxicity whereas all toxic noniron metalloporphyrins inhibit bacterial respiration. Finally, we demonstrate that, despite the fact that toxic metalloporphyrin treatment induces expression of
S. aureus
heme detoxification machinery, the HrtAB heme export pump is unable to detoxify most of these molecules. The ineffectiveness of HrtAB against toxic heme analogues provides an explanation for their increased antimicrobial activity relative to heme. Additionally, these studies define the specificity of HssRS/HrtAB, which may provide future insight into the biochemical mechanisms of these systems.
Defining the Region of Bacillus subtilis SpoIIIJ That Is Essential for Its Sporulation-Specific Function
Authors: Geng Yanping , de Keyzer Jeanine , Scheffers Dirk-Jan , Driessen Arnold J. M. 
Published: January 2014

ABSTRACT

Proteins of the YidC/OxaI/Alb3 family play a crucial role in the insertion, folding, and/or assembly of membrane proteins in prokaryotes and eukaryotes.
Bacillus subtilis
has two YidC-like proteins, denoted SpoIIIJ and YqjG. SpoIIIJ and YqjG are largely exchangeable in function, but SpoIIIJ has a unique role in sporulation, while YqjG stimulates competence development. To obtain more insight into the regions important for the sporulation specificity of SpoIIIJ, a series of SpoIIIJ/YqjG chimeras was constructed. These chimeras were tested for functionality during vegetative growth and for their ability to complement the sporulation defect of a
spoIIIJ
deletion strain. The data suggest an important role for the domain comprising transmembrane segment 2 (TMS2) and its flanking loops in sporulation specificity, with lesser contributions to specificity by TMS1 and TMS3.
The
ssbL
Gene Harbored by the ColV Plasmid of an Escherichia coli Neonatal Meningitis Strain Is an Auxiliary Virulence Factor Boosting the Production of Siderophores through the Shikimate Pathway
Authors: Lemaître Chloé , Bidet Philippe , Benoist Jean-François , Schlemmer Dimitri , Sobral Elsa , d'Humières Camille , Bonacorsi Stéphane 
Published: January 2014

ABSTRACT

The ability to capture iron is a challenge for most bacteria. The neonatal meningitis
Escherichia coli
strain S88 possesses several iron uptake systems, notably including siderophores. Transcriptional analysis of the ColV plasmid pS88 has shown strong induction of a previously undescribed gene with low identity to three
E. coli
chromosomal genes encoding phospho-2-dehydro-3-deoxyheptonate aldolases involved in aromatic amino acid and catecholate/phenolate siderophore biosynthesis through the shikimate pathway. Here, we investigated the role of this gene,

ssbL
p

(
ssbL
carried on the plasmid), in siderophore biosynthesis and, consequently, in S88 virulence. We constructed an S88 mutant designated S88 Δ

ssbL
p

, which exhibited reduced growth under low-iron conditions compared to the wild-type strain. Liquid chromatography-mass spectroscopy analysis of culture supernatants showed that the mutant secreted significantly smaller amounts of enterobactin, salmochelin SX, and yersiniabactin than the wild-type strain. The mutant was also less virulent in a neonatal rat sepsis model, with significantly lower bacteremia and mortality. Supplementation with chorismate, the final product of the shikimate pathway, restored the wild-type phenotype
in vitro
. In a collection of human extraintestinal
E. coli
isolates, we found that
ssbL
was present only in strains harboring the
iro
locus, encoding salmochelins, and was located either on the chromosome or on plasmids. Acquisition of the
iro
locus has been accompanied by acquisition of the auxiliary gene
ssbL
, which boosts the metabolic pathway essential for catecholate/phenolate siderophore biosynthesis and could represent potential therapeutic targets.
RecD2 Helicase Limits Replication Fork Stress in Bacillus subtilis
Authors: Walsh Brian W. , Bolz Samantha A. , Wessel Sarah R. , Schroeder Jeremy W. , Keck James L. , Simmons Lyle A. 
Published: January 2014

ABSTRACT

DNA helicases have important roles in genome maintenance. The RecD helicase has been well studied as a component of the heterotrimeric RecBCD helicase-nuclease enzyme important for double-strand break repair in
Escherichia coli
. Interestingly, many bacteria lack RecBC and instead contain a RecD2 helicase, which is not known to function as part of a larger complex. Depending on the organism studied, RecD2 has been shown to provide resistance to a broad range of DNA-damaging agents while also contributing to mismatch repair (MMR). Here we investigated the importance of
Bacillus subtilis
RecD2 helicase to genome integrity. We show that deletion of
recD2
confers a modest increase in the spontaneous mutation rate and that the mutational signature in Δ
recD2
cells is not consistent with an MMR defect, indicating a new function for RecD2 in
B. subtilis
. To further characterize the role of RecD2, we tested the deletion strain for sensitivity to DNA-damaging agents. We found that loss of RecD2 in
B. subtilis
sensitized cells to several DNA-damaging agents that can block or impair replication fork movement. Measurement of replication fork progression
in vivo
showed that forks collapse more frequently in Δ
recD2
cells, supporting the hypothesis that RecD2 is important for normal replication fork progression. Biochemical characterization of
B. subtilis
RecD2 showed that it is a 5′-3′ helicase and that it directly binds single-stranded DNA binding protein. Together, our results highlight novel roles for RecD2 in DNA replication which help to maintain replication fork integrity during normal growth and when forks encounter DNA damage.
Two Glycine Riboswitches Activate the Glycine Cleavage System Essential for Glycine Detoxification in Streptomyces griseus
Authors: Tezuka Takeaki , Ohnishi Yasuo 
Published: January 2014

ABSTRACT

The glycine cleavage (GCV) system catalyzes the oxidative cleavage of glycine into CO
2
, NH
4
+
, and a methylene group, which is accepted by tetrahydrofolate (THF) to form
N
5
,
N
10
-methylene-THF.
Streptomyces griseus
contains
gcvP
and the
gcvT-gcvH
operon, which encode three intrinsic components of the GCV system. We identified the transcriptional start sites of
gcvTH
and
gcvP
and found putative glycine riboswitches in their 5′ untranslated regions (5′ UTRs). The ratios of the transcripts of the
gcvT
and
gcvP
coding sequences (CDSs) to those of the respective 5′ UTRs were significantly higher in the presence of glycine in the wild-type strain. However, the levels of
gcvT
and
gcvP
CDS transcripts were not increased by glycine in the respective 5′ UTR deletion mutants. A reporter gene assay showed that a transcriptional terminator exists in the 5′ UTR of
gcvTH
. Furthermore, by an in-line probing assay, we confirmed that glycine bound directly to the putative riboswitch RNAs. These results indicate that the
S. griseus
glycine riboswitches enhance transcriptional read-through to the downstream CDSs, like known glycine riboswitches in other bacteria. We examined the growth of three mutants in which either or both of the
gcvTH
and
gcvP
5′ UTRs were deleted. Like the wild-type strain, all mutants grew vigorously in a medium containing 0.9% glucose as a carbon source. However, the mutants showed severely restricted growth in a medium containing 0.9% glucose and 1% glycine, while the wild-type strain grew normally. This indicates that glycine has a growth-inhibitory effect and that the GCV system plays a critical role in glycine detoxification in
S. griseus
.
Ondansetron Combined with St36 (Zusanli) acupuncture point injection for postoperative vomiting
Authors: Chen Zi Y , Lin Ling , Wang Huan H , Zhou Yong , Yan Jian Q , Huang Yi L , Guo Qu L 
Published: January 2014

Background Ondansetron, sometimes combined with acustimulation at PC6 ( Neiguan), is commonly used for preventing postoperative nausea and vomiting, but PC6 is not the only point that can be used for this purpose. Objectives To evaluate the combined effects of ondansetron and ST36 ( Zusanli) acupuncture point injection on postoperative vomiting (POV) after laparoscopic surgery. Methods A randomised, patient and assessor-blinded, placebo-controlled clinical study was conducted. One hundred and sixty patients undergoing laparoscopic surgery were randomly assigned to one of four groups: (1) group P (placebo-control): intravenous normal saline+bilateral non-acupuncture point injection of vitamin B1 (n=40); (2) group O (ondansetron): intravenous ondansetron+bilateral ST36 sham injection (n=40); (3) group A (acupuncture point injection): intravenous normal saline+bilateral acupuncture point injection at ST36 of vitamin B1 (n=40); (4) group C (combination): intravenous ondansetron+bilateral acupuncture point injection at ST36 of vitamin B1 (n=40). Interventions were made on arrival at the postanaesthesia care unit. The primary outcome was the incidence of POV within 24 h after the operation. Secondary outcomes included severity of vomiting, incidence of rescue treatment, patients’ satisfaction and the first anal exsufflation time 24 h after the operation. Results The incidence of POV within 24 h postoperative period in each group was P 33%; O 11%, A 9% and C 6%. Outcomes for all intervention groups were significantly better than that for placebo (p<0.01). For the three interventions compared with placebo, the numbers needed to treat (NNTs) were O, NNT=5; A, NNT=5 and C, NNT=4. The secondary outcomes also demonstrated greater benefits of the combined regimen, with improvement seen in all the measures. Conclusions Ondansetron, acupuncture, and ondansetron and acupuncture combined are effective prophylaxis for POV.
Changes in the rates of weight and waist circumference gain in Australian adults over time: a longitudinal cohort study
Authors: Peeters Anna , Magliano Dianna J , Backholer Kathryn , Zimmet Paul , Shaw Jonathan E 
Published: January 2014

ObjectiveTo assess in a single cohort whether annual weight and waist circumference (WC) change has varied over time.DesignLongitudinal cohort study with three surveys (1) 1999/2000; (2) 2004/2005 and (3) 2011/2012. Generalised linear mixed models with random effects were used to compare annualised weight and WC change between surveys 1 and 2 (period 1) with that between surveys 2 and 3 (period 2). Models were adjusted for age to analyse changes with time rather than age. Models were additionally adjusted for sex, education status, area-level socioeconomic disadvantage, ethnicity, body mass index, diabetes status and smoking status.SettingThe Australian Diabetes, Obesity and Lifestyle study (AusDiab)—a population-based, stratified-cluster survey of 11247 adults aged ≥25 years.Participants3351 Australian adults who attended each of three surveys and had complete measures of weight, WC and covariates.Primary outcome measuresWeight and WC were measured at each survey. Change in weight and WC was annualised for comparison between the two periods.ResultsMean weight and WC increased in both periods (0.34 kg/year, 0.43 cm/year period 1; 0.13 kg/year, 0.46 cm/year period 2). Annualised weight gain in period 2 was 0.11 kg/year (95% CI 0.06 to 0.15) less than period 1. Lesser annual weight gain between the two periods was not seen for those with greatest area-level socioeconomic disadvantage, or in men over the age of 55. In contrast, the annualised WC increase in period 2 was greater than period 1 (0.07 cm/year, 95% CI 0.01 to 0.12). The increase was greatest in men aged 55+ years and those with a greater area-level socioeconomic disadvantage.ConclusionsBetween 2004/2005 and 2011/2012, Australian adults in a national study continued to gain weight, but more slowly than 1999/2000–2004/2005. While weight gain may be slowing, this was not observed for older men or those in more disadvantaged groups, and the same cannot be said for WC.
Salt intake assessed by 24 h urinary sodium excretion in a random and opportunistic sample in Australia
Authors: Land Mary-Anne , Webster Jacqui , Christoforou Anthea , Praveen D , Jeffery Paul , Chalmers John , Smith Wayne , Woodward Mark , Barzi Federica , Nowson Caryl , Flood Victoria , Neal Bruce 
Published: January 2014

ObjectiveThe gold standard method for measuring population sodium intake is based on a 24 h urine collection carried out in a random population sample. However, because participant burden is high, response rates are typically low with less than one in four agreeing to provide specimens. At this low level of response it is possible that simply asking for volunteers would produce the same results.SettingLithgow, New South Wales, Australia.ParticipantsWe randomly selected 2152 adults and obtained usable 24 h urine samples from 306 (response rate 16%). Specimens were also collected from a further 113 volunteers. Estimated salt consumption and the costs for each strategy were compared.ResultsThe characteristics of the ‘random’ and ‘volunteer’ samples were moderately different in mean age 58 (SD 14.6 vs 49(17.7) years, respectively; p<0.001) as well as self-reported alcohol use, tobacco use, history of hypertension and prescription drug use (all p<0.04). Overall crude mean 24 h urinary salt excretion was 8.9(3.6) g/day in the random sample vs 8.5(3.3) g/day for the volunteers (p=0.42). Corresponding age-adjusted and sex-adjusted estimates were 9.2(3.3) and 8.8(3.4) g/day (p=0.29). Estimates for men 10.3(3.8) vs 9.6(3.3) g/day; (p=0.26) and women 7.6(3) vs 7.9(3.2) g/day; (p=0.43) were also similar for the two samples, as was salt excretion across age groups (p=0.72). The cost of obtaining each 24 h urine sample was two times greater for the random compared to volunteer samples ($A62 vs $A31).ConclusionsThe estimated salt consumption derived from the two samples was comparable and was not substantively different to estimates obtained from other surveys. In countries where salt is pervasive and cannot easily be avoided, estimates of consumption obtained from volunteer samples may be valid and less costly.
Patient- and surgeon-adjusted control charts for monitoring performance
Authors: Maruthappu Mahiben , Carty Matthew J , Lipsitz Stuart R , Wright John , Orgill Dennis , Duclos Antoine 
Published: January 2014

ObjectivesTo determine whether an innovative graphical tool for accurate measurement of individual surgeon performance metrics, adjusted for both surgeon-specific and patient-specific factors, significantly alters interpretation of performance data.DesignRetrospective analysis of all total knee replacements (TKRs) conducted at the host institution between 1996 and 2009. The database was randomly divided into training and testing datasets. Using multivariate generalised estimating equation regression models, the training dataset enabled generation of patient-risk and surgeon-experience adjustment factors. To simulate prospective monitoring of individual surgeon outcomes, the testing dataset was mapped on control charts. Weighted κ statistics were calculated to measure the agreement between patient-risk adjusted and fully adjusted control charts.SettingTertiary care academic hospital.ParticipantsAll patients undergoing TKR at the host institution 1996–2009.Main outcome measureOperative efficiency.Results5313 procedures were analysed. Adjusted control charts were generated using a training dataset comprising 3756 procedures performed by 13 surgeons. The operative time gradually declined by 121 min with 25 years of experience (p<0.0001). Charts were tested by monitoring four other surgeons, performing an average of 389 procedures each. Adjustment for surgeon experience significantly altered the interpretation of operative efficiency (κ=0.29 (95% CI 0.11 to 0.47)), and enhanced assessment of a surgeon's improvement or diminishment in efficiency over time. Specifically, experience adjustment inverted the interpretation of surgeon efficiency from above average to below average, or from improving to declining performance.ConclusionsAdjustment for surgeon experience is necessary for accurate interpretation of metrics over the course of a surgeon's career. Patient-adjusted and surgeon-adjusted control charts provide an accurate method of monitoring individual operative efficiency.
Cell cycle-related kinase mediates viral-host signalling to promote hepatitis B virus-associated hepatocarcinogenesis
Authors: Yu Zhuo , Gao Yue-Qiu , Feng Hai , Lee Ying-Ying , Li May S , Tian Yuan , Go Minnie Y Y , Yu Dae-Yeul , Cheung Yue-Sun , Lai Paul B S , Yu Jun , Wong Vincent W S , Sung Joseph J Y , Chan Henry L Y , Cheng Alfred S L 
Published: January 2014

BackgroundAndrogen receptor (AR) signalling contributes to male predominance in hepatocellular carcinoma (HCC), which is more pronounced in HBV-endemic areas. Cell cycle-related kinase (CCRK) is essential for AR-induced hepatocarcinogenesis but its molecular function in HBV-associated HCC remains obscure.ObjectiveTo determine the molecular function of CCRK in HBV-associated HCC.DesignTranscriptional regulation was assessed by chromatin immunoprecipitation, promoter mutation and luciferase reporter assays. Hepatocellular proliferation and tumourigenesis were examined by colony formation, soft agar assays and using HBV X protein (HBx) transgenic mice with low-dose exposure to diethylnitrosamine. Protein expressions were examined in clinical samples and correlated with patient survival by log-rank Mantel–Cox test.ResultsOverexpression of CCRK, but not its kinase-defective mutant, activated β-catenin/T cell factor signalling through phosphorylation of glycogen synthase kinase-3β (GSK-3β) at Ser9, led to upregulation of AR transcriptional activity and, subsequently, expression of HBx. The viral transactivator in turn induced CCRK expression through enhanced AR signalling, thus forming a positive regulatory loop. RNA interference silencing of CCRK, which suppressed the CCRK/GSK-3β/β-catenin/AR regulatory loop, significantly suppressed HBx-induced hepatocellular proliferation (p=0.001) and transformation (p<0.001) and remarkably reduced >80% diethylnitrosamine-mediated hepatocarcinogenesis in HBx transgenic mice. Finally, patients with HBV-associated HCC with concordant overexpression of CCRK, GSK-3β phosphorylation at Ser9, active dephosphorylated β-catenin and AR phosphorylation at Ser81 had poorer overall (HR=31.26, p<0.0001) and disease-free (HR=3.60, p<0.01) survival rates.ConclusionsOur findings highlight the critical role of CCRK in a self-reinforcing circuitry that regulates HBV-associated hepatocarcinogenesis. Further characterisation of this intricate viral-host signalling may provide new prognostic biomarkers and therapeutic targets for HCC treatment.
Do changes in objective and subjective family income predict change in children's diets over time? Unique insights using a longitudinal cohort study and fixed effects analysis
Authors: Skafida Valeria , Treanor Morag C 
Published: January 2014

BackgroundWhile an association has been established between low income and poor diet using cross-sectional data, such analysis cannot account for confounding by unobserved characteristics correlated with income and diet, and changes in income and diet cannot be tracked over time. This paper, using longitudinal panel data, explores whether falls in objective and subjective family income predict deterioration in children's diets over time.MethodsThis paper uses panel data from the nationally representative birth cohort study Growing Up in Scotland. 3279 families have valid data on all dependent, independent and control variables for both time points. Dietary data were collected using maternal recall at sweeps 2 and 5 when the children were aged 22 and 58 months, respectively. Mothers reported on children's variety of consumption of vegetables, fruit and on the frequency of consumption of crisps, sweets and sugary drinks. The dietary variables were ordinal and were analysed using multivariate fixed effects ordinal logistic regression models.ResultsControlling for time-varying confounders (children's food fussiness, maternal social class, maternal education, family composition, maternal employment) and for family and child time-invariant characteristics, moving from the highest to the lowest income band was linked to a smaller chance of increased fruit variety from 22 to 58 months (OR=0.42, 95% CI 0.21 to 0.82). Mothers who transitioned from ‘living very comfortably’ to ‘finding it very difficult’ to cope on current income had children who consumed fewer fruit varieties over time (OR=0.40, 95% CI 0.19 to 0.85), and who increased their frequency of consumption of crisps (OR=2.03, 95% CI 1.05 to 3.94) and sweets (OR=2.23, 95% CI 1.18 to 4.20).ConclusionsThe diets of young children in Scotland deteriorated between the ages of 2 and 5 years across the entire socioeconomic spectrum. Additionally, deterioration in subjective income predicted less healthy diets for children.
Correlation of clot imaging with endovascular recanalization in internal carotid artery terminus occlusion
Authors: Fujimoto Motoaki , Salamon Noriko , Takemoto Koichiro , Takao Hiroyuki , Song Ligang , Tateshima Satoshi , Viñuela Fernando 
Published: January 2014

Background and purposeIn a swine stroke model we have previously demonstrated a high-intensity fluid attenuated inversion recovery (FLAIR) signal representing the erythrocyte component of the clot. We hypothesized that the intensity of the FLAIR clot signal in patients with acute stroke may predict the efficacy of recanalization by thrombectomy devices. In this study we compared the pretreatment FLAIR signal intensity of the clots in the distal internal carotid artery (ICA) and the degree of angiographic recanalization rate after mechanical thrombectomy.Methods25 consecutive acute stroke patients with ICA terminus (ICA-T) occlusion diagnosed with MRI at the UCLA Medical Center between 2002 and 2013 were retrospectively reviewed. The intensity of the FLAIR clot signal at the distal ICA was blindly compared with the angiographic recanalization status (successful recanalization defined as Thrombolysis In Cerebral Infarction (TICI) score of 2b–3) and non-successful recanalization as TICI score 0–2a) after endovascular treatment. Multivariate logistic regression analysis for successful recanalization was performed.ResultsSuccessful recanalization was achieved in 40% of patients (10/25) and showed a significantly higher FLAIR intensity (p=0.014). The cut-off value for clot intensity on the FLAIR sequence to predict recanalization was 0.7952, with 70% sensitivity and 80% specificity (95% CI 0.59 to 0.96) using a receiver operating characteristic curve. In multivariate logistic regression analysis, only a high FLAIR clot intensity (>0.7952) was associated with successful recanalization (OR 16.79; 95% CI 1.29 to 218.92; p=0.031).ConclusionsHigh signal intensity on FLAIR clot imaging may predict successful recanalization after endovascular therapy for ICA-T occlusion.