bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of Each Cistron in the
gal
Operon Can Be Regulated by Transcription Termination and Generation of a
galK
-Specific mRNA, mK2
Authors: Wang Xun , Ji Sang Chun , Yun Sang Hoon , Jeon Heung Jin , Kim Si Wouk , Lim Heon M. 
Published: May 2014

ABSTRACT

The
gal
operon of
Escherichia coli
has 4 cistrons,
galE
,
galT
,
galK
, and
galM
. In our previous report (H. J. Lee, H. J. Jeon, S. C. Ji, S. H. Yun, H. M. Lim, J. Mol. Biol.
378:
318–327, 2008), we identified 6 different mRNA species, mE1, mE2, mT1, mK1, mK2, and mM1, in the
gal
operon and mapped these mRNAs. The mRNA map suggests a gradient of gene expression known as natural polarity. In this study, we investigated how the mRNAs are generated to understand the cause of natural polarity. Results indicated that mE1, mT1, mK1, and mM1, whose 3′ ends are located at the end of each cistron, are generated by transcription termination. Since each transcription termination is operating with a certain frequency and those 4 mRNAs have 5′ ends at the transcription initiation site(s), these transcription terminations are the basic cause of natural polarity. Transcription terminations at
galE-galT
and
galT-galK
junctions, making mE1 and mT1, are Rho dependent. However, the terminations to make mK1 and mM1 are partially Rho dependent. The 5′ ends of mK2 are generated by an endonucleolytic cleavage of a pre-mK2 by RNase P, and the 3′ ends are generated by Rho termination 260 nucleotides before the end of the operon. The 5′ portion of pre-mK2 is likely to become mE2. These results also suggested that
galK
expression could be regulated through mK2 production independent from natural polarity.
Streptococcus pyogenes Polymyxin B-Resistant Mutants Display Enhanced ExPortal Integrity
Authors: Port Gary C. , Vega Luis A. , Nylander Andrew B. , Caparon Michael G. 
Published: May 2014

ABSTRACT

The ExPortal protein secretion organelle in
Streptococcus pyogenes
is an anionic phospholipid-containing membrane microdomain enriched in Sec translocons and postsecretion protein biogenesis factors. Polymyxin B binds to and disrupts ExPortal integrity, resulting in defective secretion of several toxins. To gain insight into factors that influence ExPortal organization, a genetic screen was conducted to select for spontaneous polymyxin B-resistant mutants displaying enhanced ExPortal integrity. Whole-genome resequencing of 25 resistant mutants revealed from one to four mutations per mutant genome clustered primarily within a core set of 10 gene groups. Construction of mutants with individual deletions or insertions demonstrated that 7 core genes confer resistance and enhanced ExPortal integrity through loss of function, while 3 were likely due to gain of function and/or combinatorial effects. Core resistance genes include a transcriptional regulator of lipid biosynthesis, several genes involved in nutrient acquisition, and a variety of genes involved in stress responses. Two members of the latter class also function as novel regulators of the secreted SpeB cysteine protease. Analysis of the most frequently isolated mutation, a single nucleotide deletion in a track of 9 consecutive adenine residues in
pstS
, encoding a component of a high-affinity P
i
transporter, suggests that this sequence functions as a molecular switch to facilitate stress adaptation. Together, these data suggest the existence of a membrane stress response that promotes enhanced ExPortal integrity and resistance to cationic antimicrobial peptides.
NtrBC and Nac Contribute to Efficient Shigella flexneri Intracellular Replication
Authors: Waddell Chelsea D. , Walter Thomas J. , Pacheco Sophia A. , Purdy Georgiana E. , Runyen-Janecky Laura J. 
Published: May 2014

ABSTRACTShigella flexneritwo-component regulatory systems (TCRS) are responsible for sensing changes in environmental conditions and regulating gene expression accordingly. We examined 12 TCRS that were previously uncharacterized for potential roles inS. flexnerigrowth within the eukaryotic intracellular environment. We demonstrate that the TCRS EvgSA, NtrBC, and RstBA systems are required for wild-type plaque formation in cultured epithelial cells. The phenotype of the NtrBC mutant depended in part on the Nac transcriptional regulator. Microarray analysis was performed to identifyS. flexnerigenes differentially regulated by the NtrBC system or Nac in the intracellular environment. This study contributes to our understanding of the transcriptional regulation necessary forShigellato effectively adapt to the mammalian host cell.
A Putative Bifunctional Histidine Kinase/Phosphatase of the HWE Family Exerts Positive and Negative Control on the Sinorhizobium meliloti General Stress Response
Authors: Sauviac Laurent , Bruand Claude 
Published: May 2014

ABSTRACT

The EcfG-type sigma factor RpoE2 is the regulator of the general stress response in
Sinorhizobium meliloti
. RpoE2 activity is negatively regulated by two NepR-type anti-sigma factors (RsiA1/A2), themselves under the control of two anti-anti-sigma factors (RsiB1/B2) belonging to the PhyR family of response regulators. The current model of RpoE2 activation suggests that in response to stress, RsiB1/B2 are activated by phosphorylation of an aspartate residue in their receiver domain. Once activated, RsiB1/B2 become able to interact with the anti-sigma factors and release RpoE2, which can then associate with the RNA polymerase to transcribe its target genes. The purpose of this work was to identify and characterize proteins involved in controlling the phosphorylation status of RsiB1/B2. Using
in vivo
approaches, we show that the putative histidine kinase encoded by the
rsiC
gene (SMc01507), located downstream from
rpoE2
, is able to both positively and negatively regulate the general stress response. In addition, our data suggest that the negative action of RsiC results from inhibition of RsiB1/B2 phosphorylation. From these observations, we propose that RsiC is a bifunctional histidine kinase/phosphatase responsible for RsiB1/B2 phosphorylation or dephosphorylation in the presence or absence of stress, respectively. Two proteins were previously proposed to control PhyR phosphorylation in
Caulobacter crescentus
and
Sphingomonas
sp. strain FR1. However, these proteins contain a Pfam:HisKA_2 domain of dimerization and histidine phosphotransfer, whereas
S. meliloti
RsiC harbors a Pfam:HWE_HK domain instead. Therefore, this is the first report of an HWE_HK-containing protein controlling the general stress response in
Alphaproteobacteria
.
The Terminal Oxidase
cbb
3
Functions in Redox Control of Magnetite Biomineralization in Magnetospirillum gryphiswaldense
Authors: Li Yingjie , Raschdorf Oliver , Silva Karen T. , Schüler Dirk 
Published: May 2014

ABSTRACT

The biomineralization of magnetosomes in
Magnetospirillum gryphiswaldense
and other magnetotactic bacteria occurs only under suboxic conditions. However, the mechanism of oxygen regulation and redox control of biosynthesis of the mixed-valence iron oxide magnetite [FeII(FeIII)
2
O
4
] is still unclear. Here, we set out to investigate the role of aerobic respiration in both energy metabolism and magnetite biomineralization of
M. gryphiswaldense
. Although three operons encoding putative terminal
cbb
3
-type,
aa
3
-type, and
bd
-type oxidases were identified in the genome assembly of
M. gryphiswaldense
, genetic and biochemical analyses revealed that only
cbb
3
and
bd
are required for oxygen respiration, whereas
aa
3
had no physiological significance under the tested conditions. While the loss of
bd
had no effects on growth and magnetosome synthesis, inactivation of
cbb
3
caused pleiotropic effects under microaerobic conditions in the presence of nitrate. In addition to their incapability of simultaneous nitrate and oxygen reduction,
cbb
3
-deficient cells had complex magnetosome phenotypes and aberrant morphologies, probably by disturbing the redox balance required for proper growth and magnetite biomineralization. Altogether, besides being the primary terminal oxidase for aerobic respiration,
cbb
3
oxidase may serve as an oxygen sensor and have a further role in poising proper redox conditions required for magnetite biomineralization.
Novel MntR-Independent Mechanism of Manganese Homeostasis in Escherichia coli by the Ribosome-Associated Protein HflX
Authors: Kaur Gursharan , Sengupta Sandeepan , Kumar Vineet , Kumari Aruna , Ghosh Aditi , Parrack Pradeep , Dutta Dipak 
Published: May 2014

ABSTRACT

Manganese is a micronutrient required for activities of several important enzymes under conditions of oxidative stress and iron starvation. In
Escherichia coli
, the manganese homeostasis network primarily constitutes a manganese importer (MntH) and an exporter (MntP), which are regulated by the MntR dual regulator. In this study, we find that deletion of
E. coli
hflX
, which encodes a ribosome-associated GTPase with unknown function, renders extreme manganese sensitivity characterized by arrested cell growth, filamentation, lower rate of replication, and DNA damage. We demonstrate that perturbation by manganese induces unprecedented influx of manganese in Δ
hflX
cells compared to that in the wild-type
E. coli
strain. Interestingly, our study indicates that the imbalance in manganese homeostasis in the Δ
hflX
strain is independent of the MntR regulon. Moreover, the influx of manganese leads to a simultaneous influx of zinc and inhibition of iron import in Δ
hflX
cells. In order to review a possible link of HflX with the λ phage life cycle, we performed a lysis-lysogeny assay to show that the Mn-perturbed Δ
hflX
strain reduces the frequency of lysogenization of the phage. This observation raises the possibility that the induced zinc influx in the manganese-perturbed Δ
hflX
strain stimulates the activity of the zinc-metalloprotease HflB, the key determinant of the lysis-lysogeny switch. Finally, we propose that manganese-mediated autophosphorylation of HflX plays a central role in manganese, zinc, and iron homeostasis in
E. coli
cells.
Risk factors for groin/hip injuries in field-based sports: a systematic review
Authors: Ryan Julianne , DeBurca Neasa , Mc Creesh Karen 
Published: May 2014

BackgroundGroin/hip injuries are common in the athletic population, particularly in sports requiring kicking, twisting, turning and rapid acceleration and deceleration. Chronic hip, buttock and groin pain account for 10% of all attendances to sports medicine centres. Understanding risk factors for field-based sports (FBS) players is important in developing preventive measures for injury.ObjectiveThis systematic review aims to identify and examine the evidence for groin/hip injury risk factors in FBS.Methods14 electronic databases were searched using keywords. Studies were included if they met the inclusion criteria and investigated one or more risk factors with relation to the incidence of groin/hip injuries in FBS. Studies were accumulated and independently analysed by two reviewers under a 12-point quality assessment scale (modified CASP (for cohort study design) assessment scale). Owing to the heterogeneity of studies and measures used, a meta-analysis could not be conducted. As a result risk factors were pooled for analysis and discussion.ResultsOf the 5842 potentially relevant studies, 7 high-quality studies were included in this review. Results demonstrated that previous groin/hip injury was the most prominent risk factor, identified across four studies (OR range from 2.6 (95% CI 1.1 to 6.11) to 7.3, (p=0.001)), followed by older age (OR 0.9, p=0.05) and weak adductor muscles (OR 4.28, 95% CI 1.31 to 14.0, p=0.02) each identified in two studies. Eight other significant risk factors were identified once across the included studies.Conclusions11 significant risk factors for groin/hip injury for FBS players were identified. The most prominent risk factor identified was previous groin/hip injury. Future research should include a prospective study of a group of FBS players to confirm a relationship between the risk factors identified and development of groin/hip injuries.
The use and impact of cancer medicines in routine clinical care: methods and observations in a cohort of elderly Australians
Authors: Pearson Sallie-Anne , Schaffer Andrea 
Published: May 2014

IntroductionAfter medicines have been subsidised in Australia we know little about their use in routine clinical practice, impact on resource utilisation, effectiveness or safety. Routinely collected administrative health data are available to address these issues in large population-based pharmacoepidemiological studies. By bringing together cross-jurisdictional data collections that link drug exposure to real-world outcomes, this research programme aims to evaluate the use and impact of cancer medicines in a subset of elderly Australians in the real-world clinical setting.Methods and analysisThis ongoing research programme involves a series of retrospective cohort studies of Australian Government Department of Veterans’ Affairs (DVA) clients. The study population includes 104 635 veterans who reside in New South Wales, Australia, and were aged 65 years and over as of 1 July 2004. We will investigate trends in cancer medicines use according to cancer type and other sociodemographic characteristics as well as predictors of the initiation of cancer medicines and other treatment modalities, survival and adverse outcomes among patients with cancer. The programme is underpinned by the linkage of eight health administrative databases under the custodianship of the DVA and the New South Wales Ministry of Health, including cancer notifications, medicines dispensing data, hospitalisation data and health services data. The cancer notifications database is available from 1994 with all other databases available from 2005 onwards.Ethics and disseminationEthics approval has been granted by the DVA and New South Wales Population and Health Service Research Ethics Committees.ResultsResults will be reported in peer-reviewed publications, conference presentations and policy forums. The programme has high translational potential, providing invaluable evidence about cancer medicines in an elderly population who are under-represented in clinical trials.
Age, occupational class and sickness absence during pregnancy: a retrospective analysis study of the Norwegian population registry
Authors: Ariansen Anja M S 
Published: May 2014

ObjectiveWestern women increasingly delay having children to advance their career, and pregnancy is considered to be riskier among older women. In Norway, this development surprisingly coincides with increased sickness absence among young pregnant women, rather than their older counterparts. This paper tests the hypothesis that young pregnant women have a higher number of sick days because this age group includes a higher proportion of working class women, who are more prone to sickness absence.DesignA zero-inflated Poisson regression was conducted on the Norwegian population registry.ParticipantsAll pregnant employees giving birth in 2004–2008 were included in the study. A total number of 216 541 pregnancies were observed among 180 483 women.Outcome measureNumber of sick days.ResultsAlthough the association between age and number of sick days was U-shaped, pregnant women in their early 20s had a higher number of sick days than those in their mid-40s. This was particularly the case for pregnant women with previous births. In this group, 20-year-olds had 12.6 more sick days than 45-year-olds; this age difference was reduced to 6.3 after control for class. Among women undergoing their first pregnancy, 20-year-olds initially had 1.2 more sick days than 45-year-olds, but control for class altered this age difference. After control for class, 45-year-old first-time pregnant women had 2.9 more sick days than 20-year-olds with corresponding characteristics.ConclusionsThe negative association between age and sickness absence was partly due to younger age groups including more working class women, who were more prone to sickness absence. Young pregnant women's needs for job adjustments should not be underestimated.
Should vitamin B12tablets be included in more Canadian drug formularies? An economic model of the cost-saving potential from increased utilisation of oral versus intramuscular vitamin B12maintenance therapy for Alberta seniors
Authors: Houle Sherilyn K D , Kolber Michael R , Chuck Anderson W 
Published: May 2014

ObjectiveThe aim of this study was to estimate the cost-savings attainable if all patients aged ≥65 years in Alberta, Canada, currently on intramuscular therapy were switched to oral therapy, from the perspective of a provincial ministry of health.SettingPrimary care setting in Alberta, Canada.ParticipantsSeniors of age 65 years and older currently receiving intramuscular vitamin B12therapy.InterventionOral vitamin B12therapy at 1000 μg/day versus intramuscular therapy at 1000 μg/month.Primary and secondary outcome measuresCost saving from oral therapy over intramuscular therapy, from the perspective of the Alberta Ministry of Health, including drug costs, dispensing fees, injection administration fees, additional laboratory monitoring and physician visit fees.ResultsOver 5 years, if all Albertans aged 65 years and older who currently receive intramuscular B12are switched to oral therapy, our model found that $C13 975 883 can be saved. Even if no additional physician visits are billed for among patients receiving intramuscular therapy, $C8 444 346 could be saved from reduced administration costs alone.ConclusionsOral B12therapy has been shown to be an effective therapeutic option for patients with vitamin B12deficiency, yet only three provinces and the Non-Insured Health Benefits program include oral tablets on their formulary rather than the parenteral preparation. To ensure judicious use of limited health resources, clinicians and formulary committees are encouraged to adopt oral B12therapy as a clinically and cost-effective first-line therapy for vitamin B12deficiency.
Risk factors for exposure of glaucoma drainage devices: a retrospective observational study
Authors: Muir Kelly W , Lim Annie , Stinnett Sandra , Kuo Anthony , Tseng Henry , Walsh Molly M 
Published: May 2014

ObjectivesThe purpose of this study was to identify risk factors for exposure of glaucoma drainage devices (GDD).SettingThis retrospective, observational study was conducted in the eye clinic of an academic medical centre.ParticipantsParticipants included 1073 consecutive adults who underwent GDD surgery between 1 January 2005 and 1 January 2011. Participants were included if chart review indicated GDD surgery during the study period and excluded if at least 12 months of clinical follow-up was not available in the medical record.Primary outcome measureThe primary outcome measure was exposure of the GDD occurring at least 1 month after implant surgery. The characteristics of participants who experienced exposure of the implant were compared to the characteristics of participants who did not experience exposure.ResultsOf the 1073 participants having undergone GDD surgery, 67 experienced exposure of the device. Neither the type of GDD, type of patch graft (eye bank sclera, Tutoplast sclera and Tutoplast pericardium), surgeon, location of GDD, number of GDD previously implanted into the eye, nor history of diabetes or uveitis were associated with likelihood of exposure. Women were more likely than men to experience exposure of the GDD (OR 2.004 (95% CI1.170 to 3.431)) in both univariable (p=0.011) and multivariable (p=0.013) analyses. In survival analysis, exposure of the GDD occurred earlier for women than for men (58 vs 61 months; p=0.024).White race (vs black) was also associated with increased risk of GDD exposure (OR 1.693 (95% CI 1.011 to 2.833)) in univariable (p=0.044) and multivariable (p=0.046) analyses.ConclusionsWomen are two times more likely to experience GDD exposure than men, independent of age. White race is also a risk factor for exposure.
Triage tests for identifying atrial fibrillation in primary care: a diagnostic accuracy study comparing single-lead ECG and modified BP monitors
Authors: Kearley Karen , Selwood Mary , Van den Bruel Ann , Thompson Matthew , Mant David , Hobbs FD Richard , Fitzmaurice David , Heneghan Carl 
Published: May 2014

ObjectiveNew electronic devices offer an opportunity within routine primary care settings for improving the detection of atrial fibrillation (AF), which is a common cardiac arrhythmia and a modifiable risk factor for stroke. We aimed to assess the performance of a modified blood pressure (BP) monitor and two single-lead ECG devices, as diagnostic triage tests for the detection of AF.Setting6 General Practices in the UK.Participants1000 ambulatory patients aged 75 years and over.Primary and secondary outcome measuresComparative diagnostic accuracy of modified BP monitor and single-lead ECG devices, compared to reference standard of 12-lead ECG, independently interpreted by cardiologists.ResultsA total of 79 participants (7.9%) had AF diagnosed by 12-lead ECG. All three devices had a high sensitivity (93.9–98.7%) and are useful for ruling out AF. WatchBP is a better triage test than Omron autoanalysis because it is more specific—89.7% (95% CI 87.5% to 91.6%) compared to 78.3% (95% CI 73.0% to 82.9%), respectively. This would translate into a lower follow-on ECG rate of 17% to rule in/rule out AF compared to 29.7% with the Omron text message in the study population. The overall specificity of single-lead ECGs analysed by a cardiologist was 94.6% for Omron and 90.1% for Merlin.ConclusionsWatchBP performs better as a triage test for identifying AF in primary care than the single-lead ECG monitors as it does not require expertise for interpretation and its diagnostic performance is comparable to single-lead ECG analysis by cardiologists. It could be used opportunistically to screen elderly patients for undiagnosed AF at regular intervals and/or during BP measurement.
Sex-specific trends in 4-year survival in 37 276 men and women with acute myocardial infarction before the age of 55 years in Sweden, 1987–2006: a register-based cohort study
Authors: Nielsen S , Björck L , Berg J , Giang K W , Zverkova Sandström T , Falk K , Määttä S , Rosengren A 
Published: May 2014

ObjectiveTo examine sex-specific trends in 4-year mortality among young patients with first acute myocardial infarction (AMI), 1987–2006.DesignProspective cohort study.SettingSweden.ParticipantsWe identified 37 276 cases (19.4% women; age, 25–54 years) from the Swedish Inpatient Register, 1987–2006, who had survived 28 days after an AMI.Outcome measures4-year mortality from all causes and standard mortality ratio (SMR).ResultsFrom the first to last 5-year period, the absolute excess risk decreased from 1.38 to 0.50 and 1.53 to 0.59 per 100 person-years among men aged 25–44 and 45–54 years, respectively. Corresponding figures for women were a decrease from 2.26 to 1.17 and from 1.93 to 1.45 per 100 person-years, respectively. Trends for women were non-linear, decreasing to the same extent as those for men until the third period, then increasing. For the last 5-year period, the standardised mortality ratio for young survivors of AMI compared with the general population was 4.34 (95% CI 3.04 to 5.87) and 2.43 (95% CI 2.12 to 2.76) for men aged 25–44 and 45–54 years, respectively, and 13.53 (95% CI 8.36 to 19.93) and 6.42 (95% CI 5.24 to 7.73) for women, respectively. Deaths not associated with cardiovascular causes increased from 21.5% to 44.6% in men and 41.5% to 65.9% in women.ConclusionsYoung male survivors of AMI have low absolute long-term mortality rates, but these rates remain twofold to fourfold that of the general population. After favourable development until 2001, women now have higher absolute mortality than men and a 6-fold to 14-fold risk of death compared with women in the general population.