bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multilocus Sequence Typing Identifies Epidemic Clones of Flavobacterium psychrophilum in Nordic Countries
Authors: Nilsen Hanne , Sundell Krister , Duchaud Eric , Nicolas Pierre , Dalsgaard Inger , Madsen Lone , Aspán Anna , Jansson Eva , Colquhoun Duncan J. , Wiklund Tom 
Published: February 2014

ABSTRACT

Flavobacterium psychrophilum
is the causative agent of bacterial cold water disease (BCWD), which affects a variety of freshwater-reared salmonid species. A large-scale study was performed to investigate the genetic diversity of
F. psychrophilum
in the four Nordic countries: Denmark, Finland, Norway, and Sweden. Multilocus sequence typing of 560 geographically and temporally disparate
F. psychrophilum
isolates collected from various sources between 1983 and 2012 revealed 81 different sequence types (STs) belonging to 12 clonal complexes (CCs) and 30 singleton STs. The largest CC, CC-ST10, which represented almost exclusively isolates from rainbow trout and included the most predominant genotype, ST2, comprised 65% of all isolates examined. In Norway, with a shorter history (<10 years) of BCWD in rainbow trout, ST2 was the only isolated CC-ST10 genotype, suggesting a recent introduction of an epidemic clone. The study identified five additional CCs shared between countries and five country-specific CCs, some with apparent host specificity. Almost 80% of the singleton STs were isolated from non-rainbow trout species or the environment. The present study reveals a simultaneous presence of genetically distinct CCs in the Nordic countries and points out specific
F. psychrophilum
STs posing a threat to the salmonid production. The study provides a significant contribution toward mapping the genetic diversity of
F. psychrophilum
globally and support for the existence of an epidemic population structure where recombination is a significant driver in
F. psychrophilum
evolution. Evidence indicating dissemination of a putatively virulent clonal complex (CC-ST10) with commercial movement of fish or fish products is strengthened.
Multiple Nuclear Localization Signals Mediate Nuclear Localization of the GATA Transcription Factor AreA
Authors: Hunter Cameron C. , Siebert Kendra S. , Downes Damien J. , Wong Koon Ho , Kreutzberger Sara D. , Fraser James A. , Clarke David F. , Hynes Michael J. , Davis Meryl A. , Todd Richard B. 
Published: February 2014

ABSTRACT

The
Aspergillus nidulans
GATA transcription factor AreA activates transcription of nitrogen metabolic genes in response to nitrogen limitation and is known to accumulate in the nucleus during nitrogen starvation. Sequence analysis of AreA revealed multiple nuclear localization signals (NLSs), five putative classical NLSs conserved in fungal AreA orthologs but not in the
Saccharomyces cerevisiae
functional orthologs Gln3p and Gat1p, and one putative noncanonical RRX
33
RXR bipartite NLS within the DNA-binding domain. In order to identify the functional NLSs in AreA, we constructed
areA
mutants with mutations in individual putative NLSs or combinations of putative NLSs and strains expressing green fluorescent protein (GFP)-AreA NLS fusion genes. Deletion of all five classical NLSs individually or collectively did not affect utilization of nitrogen sources or AreA-dependent gene expression and did not prevent AreA nuclear localization. Mutation of the bipartite NLS conferred the inability to utilize alternative nitrogen sources and abolished AreA-dependent gene expression likely due to effects on DNA binding but did not prevent AreA nuclear localization. Mutation of all six NLSs simultaneously prevented AreA nuclear accumulation. The bipartite NLS alone strongly directed GFP to the nucleus, whereas the classical NLSs collaborated to direct GFP to the nucleus. Therefore, AreA contains multiple conserved NLSs, which show redundancy and together function to mediate nuclear import. The noncanonical bipartite NLS is conserved in GATA factors from
Aspergillus
, yeast, and mammals, indicating an ancient origin.
The C-Terminal Part of Microcin B Is Crucial for DNA Gyrase Inhibition and Antibiotic Uptake by Sensitive Cells
Authors: Shkundina Irina , Serebryakova Marina , Severinov Konstantin 
Published: February 2014

ABSTRACT

Microcin B (McB) is a ribosomally synthesized antibacterial peptide. It contains up to nine oxazole and thiazole heterocycles that are introduced posttranslationally and are required for activity. McB inhibits the DNA gyrase, a validated drug target. Previous structure-activity analyses indicated that two fused heterocycles located in the central part of McB are important for antibacterial action and gyrase inhibition. Here, we used site-specific mutagenesis of the McB precursor gene to assess the functional significance of the C-terminal part of McB that is located past the second fused heterocycle and contains two single heterocycles as well as an unmodified four-amino-acid C-terminal tail. We found that removal of unmodified C-terminal amino acids of McB, while having no effect on fused heterocycles, has a very strong negative effect on activity
in vivo
and
in vitro
. In fact, even nonconservative point substitutions in the last McB amino acid have a very strong effect by simultaneously decreasing uptake and ability to inhibit the gyrase. The results highlight the importance of unmodified McB amino acids for function and open the way for creation of recombinant McB derivatives with an altered or expanded spectrum of antibacterial action.
The PhoU Protein from Escherichia coli Interacts with PhoR, PstB, and Metals To Form a Phosphate-Signaling Complex at the Membrane
Authors: Gardner Stewart G. , Johns Kristine D. , Tanner Rebecca , McCleary William R. 
Published: February 2014

ABSTRACT

Robust growth in many bacteria is dependent upon proper regulation of the adaptive response to phosphate (P
i
) limitation. This response enables cells to acquire P
i
with high affinity and utilize alternate phosphorous sources. The molecular mechanisms of P
i
signal transduction are not completely understood. PhoU, along with the high-affinity, P
i
-specific ATP-binding cassette transporter PstSCAB and the two-component proteins PhoR and PhoB, is absolutely required for P
i
signaling in
Escherichia coli
. Little is known about the role of PhoU and its function in regulation. We have demonstrated using bacterial two-hybrid analysis and confirmatory coelution experiments that PhoU interacts with PhoR through its PAS (
P
er-
A
RNT-
S
im) domain and that it also interacts with PstB, the cytoplasmic component of the transporter. We have also shown that the soluble form of PhoU is a dimer that binds manganese and magnesium. Alteration of highly conserved residues in PhoU by site-directed mutagenesis shows that these sites play a role in binding metals. Analysis of these
phoU
mutants suggests that metal binding may be important for PhoU membrane interactions. Taken together, these results support the hypothesis that PhoU is involved in the formation of a signaling complex at the cytoplasmic membrane that responds to environmental P
i
levels.
Escherichia coli Isolate for Studying Colonization of the Mouse Intestine and Its Application to Two-Component Signaling Knockouts
Authors: Lasaro Melissa , Liu Zhi , Bishar Rima , Kelly Kathryn , Chattopadhyay Sujay , Paul Sandip , Sokurenko Evgeni , Zhu Jun , Goulian Mark 
Published: February 2014

ABSTRACT

The biology of
Escherichia coli
in its primary niche, the animal intestinal tract, is remarkably unexplored. Studies with the streptomycin-treated mouse model have produced important insights into the metabolic requirements for
Escherichia coli
to colonize mice. However, we still know relatively little about the physiology of this bacterium growing in the complex environment of an intestine that is permissive for the growth of competing flora. We have developed a system for studying colonization using an
E. coli
strain, MP1, isolated from a mouse. MP1 is genetically tractable and does not require continuous antibiotic treatment for stable colonization. As an application of this system, we separately knocked out each two-component system response regulator in MP1 and performed competitions against the wild-type strain. We found that only three response regulators, ArcA, CpxR, and RcsB, produce strong colonization defects, suggesting that in addition to anaerobiosis, adaptation to cell envelope stress is a critical requirement for
E. coli
colonization of the mouse intestine. We also show that the response regulator OmpR, which had previously been hypothesized to be important for adaptation between
in vivo
and
ex vivo
environments, is not required for MP1 colonization due to the presence of a third major porin.
Anterior cruciate ligament injury alters preinjury lower extremity biomechanics in the injured and uninjured leg: the JUMP-ACL study
Authors: Goerger Benjamin M , Marshall Stephen W , Beutler Anthony I , Blackburn J Troy , Wilckens John H , Padua Darin A 
Published: February 2014

BackgroundInformation as to how anterior cruciate ligament (ACL) injury and reconstructive surgery (ACLR) alter lower extremity biomechanics may improve rehabilitation and return to play guidelines, reducing the risk for repeat ACL injury.AimTo compare lower extremity biomechanics before ACL injury and after subsequent ACLR for the injured and uninjured leg.MethodsBaseline unilateral lower extremity biomechanics were collected on the dominant leg of participants without ACL injury when they entered the Joint Undertaking to Monitor and Prevent ACL (JUMP-ACL) study. Thirty-one participants with subsequent ACL injury, reconstructive surgery and full return to physical activity completed repeat, follow-up biomechanical testing, as did 39 uninjured, matched controls. Not all injured participants suffered injury to the dominant leg, requiring separation of those with ACL injury into two groups: ACLR-injured leg group (n=12) and ACLR-uninjured leg group (n=19). We compared the landing biomechanics of these three groups (ACLR-injured leg, ACLR-uninjured leg, control) before ACL injury (baseline) with biomechanics after ACL injury, surgery and return to physical activity (follow-up).ResultsACL injury and ACLR altered lower extremity biomechanics, as both ACLR groups demonstrated increases in frontal plane movement (increased hip adduction and knee valgus). The ACLR-injured leg group also exhibited decreased sagittal plane loading (decreased anterior tibial shear force, knee extension moment and hip flexion moment). No high-risk biomechanical changes were observed in control group participants.ConclusionsACL injury and ACLR caused movement pattern alterations of the injured and uninjured leg that have previously shown to increase the risk for future non-contact ACL injury.
Strong evidence against platelet-rich plasma injections for chronic lateral epicondylar tendinopathy: a systematic review
Authors: de Vos Robert-Jan , Windt Johann , Weir Adam 
Published: February 2014

BackgroundChronic lateral epicondylar tendinopathy is frequent in athletes, and platelet-rich plasma (PRP) is being used increasingly in its treatment.ObjectiveTo systematically review the literature on the efficacy of PRP injections for chronic lateral epicondylar tendinopathy.MethodsThe databases of PubMed, EMBASE, CINAHL, Medline OvidSP, Scopus, Google Scholar, Web of Science and Cochrane Library were searched in October 2013. Inclusion criteria were a clinical diagnosis of chronic lateral epicondylar tendinopathy, a randomised controlled trial, an intervention with a PRP injection and the outcome measures described in terms of pain and/or function. One author screened the search results and two authors independently assessed the study quality using the Physiotherapy Evidence Database (PEDro) score. A study was considered to be of high quality if its PEDro score was ≥6. A best evidence synthesis was used to identify the level of evidence.Results6 studies were included, of which four were considered to be of high quality. Three high-quality studies (75%) and two low-quality studies showed no significant benefit at the final follow-up measurement or predefined primary outcome score when compared with a control group. One high-quality study (25%) showed a beneficial effect of a PRP injection when compared with a corticosteroid injection (corticosteroid injections are harmful in tendinopathy). Based on the best evidence synthesis, there is strong evidence that PRP injections are not efficacious in chronic lateral epicondylar tendinopathy.ConclusionsThere is strong evidence that PRP injections are not efficacious in the management of chronic lateral elbow tendinopathy.
Visual or computer-based measurements: important for interpretation of athletes’ ECG
Authors: Berge H M , Steine K , Andersen T E , Solberg E E , Gjesdal K 
Published: February 2014

BackgroundECG is recommended for preparticipation health examination in athletes. Owing to a lack of consensus on how to read and interpret athletes’ ECGs, different criteria for abnormality are used.AimsTo compare the prevalence of abnormal ECGs and test the correlation between visual and computer-based measurements.MethodsIn a preparticipation cardiac screening examination of 595 male professional soccer players aged 18–38 years, ECGs were categorised according to the European Society of Cardiology's (ESC) recommendations and the Seattle criteria, respectively. Visual measurements were conducted with callipers on-screen on the averaged PQRST complex in each lead, calculated by the trimmed mean. Computer-based measurements were derived from the medium beat. Heart rhythm and conduction were scored visually by a cardiologist. Categorical variables were compared by κ statistics (K) and continuous variables by intraclass correlation.ResultsECGs of good quality were available from 579 players. According to the ESC's recommendations and Seattle criteria, respectively, ECGs were categorised as abnormal in 171 (29.5%) vs 64 (11.1%) players after visual assessment, and in 293 (50.6%; K=0.395) vs 127 (21.9%; K=0.564) after computer-based measurements. Intraclass correlation was very good for measurements of R and S wave amplitudes and moderate to very good for intervals. K was very good for pathological Q wave amplitudes and moderate for T wave inversions.ConclusionsAbnormal ECGs were more than twice as common after computer-based than after visual measurements. Such a difference will markedly influence the number of athletes who need further examinations. Reference values may need adjustments dependent on measurement methods.
Which lipid measurement should we monitor? An analysis of the LIPID study
Authors: Glasziou Paul P , Irwig Les , Kirby Adrienne C , Tonkin Andrew M , Simes R John 
Published: February 2014

ObjectivesTo evaluate the optimal lipid to measure in monitoring patients, we assessed three factors that influence the choice of monitoring tests: (1) clinical validity; (2) responsiveness to therapy changes and (3) the size of the long-term ‘signal-to-noise’ ratio.DesignLongitudinal analyses of repeated lipid measurement over 5 years.SettingSubsidiary analysis of a Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) study—a clinical trial in Australia, New Zealand and Finland.Participants9014 patients aged 31–75 years with previous acute coronary syndromes.InterventionsPatients were randomly assigned to 40 mg daily pravastatin or placebo.Primary and secondary outcome measuresWe used data on serial lipid measurements—at randomisation, 6 months and 12 months, and then annually to 5 years—of total cholesterol; low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and their ratios; triglycerides; and apolipoproteins A and B and their ratio and their ability to predict coronary events.ResultsAll the lipid measures were statistically significantly associated with future coronary events, but the associations between each of the three ratio measures (total or LDL cholesterol to HDL cholesterol, and apolipoprotein B to apolipoprotein A1) and the time to a coronary event were better than those for any of the single lipid measures. The two cholesterol ratios also ranked highly for the long-term signal-to-noise ratios. However, LDL cholesterol and non-HDL cholesterol showed the most responsiveness to treatment change.ConclusionsLipid monitoring is increasingly common, but current guidelines vary. No single measure was best on all three criteria. Total cholesterol did not rank highly on any single criterion. However, measurements based on cholesterol subfractions—non-HDL cholesterol (total cholesterol minus HDL cholesterol) and the two ratios—appeared superior to total cholesterol or any of the apolipoprotein options. Guidelines should consider using non-HDL cholesterol or a ratio measure for initial treatment decisions and subsequent monitoring.
The routine collection of patient-reported outcome measures (PROMs) for long-term conditions in primary care: a cohort survey
Authors: Peters Michele , Crocker Helen , Jenkinson Crispin , Doll Helen , Fitzpatrick Ray 
Published: February 2014

ObjectivesTo evaluate the feasibility of using patient-reported outcome measures (PROMs) for long-term conditions (LTCs) in primary care.DesignA cohort postal survey conducted from September 2010 to April 2012.SettingPrimary care practices (n=33) in London and the North-West of England.Participants4484 patients with a diagnosis of asthma, chronic obstructive pulmonary disease, diabetes, epilepsy, heart failure or stroke were sent a survey at baseline.Main outcomeThe main outcome was to evaluate the feasibility of and the recruitment strategies for collecting PROMs data in LTCs by assessing the response rates for the baseline and follow-up surveys. Secondary outcomes were the evaluation of change scores of the EQ-5D index and visual analogue scale (VAS) between baseline and follow-up surveys.ResultsThe baseline survey achieved a response rate of 38.4% (n=1721/4485) and at follow-up 71.5% (n=1136/1589). Response rates varied by LTC. Little change was found in health-related quality of life for the total sample (−0.001 for the EQ-5D index score and 0.12 for the EQ-5D VAS) between patients responding to both the baseline and follow-up surveys.ConclusionsThe response rate to the baseline survey was similar to that of other general practice surveys. Current UK policy aims to assess health service performance in LTCs by means of using PROMs. It thus would be desirable to improve response rates by making the invitation to self-reports of health-related quality of life more engaging for patients. Results on the EQ-5D score raise questions about optimal indicators for LTCs and appropriate timelines for assessment.
Non-aristolochic acid prescribed Chinese herbal medicines and the risk of mortality in patients with chronic kidney disease: results from a population-based follow-up study
Authors: Hsieh Chuan Fa , Huang Song Lih , Chen Chien Lung , Chen Wei Ta , Chang Huan Cheng , Yang Chen Chang 
Published: February 2014

ObjectivesTo evaluate the relationship between the use of non-aristolochic acid (AA) prescribed Chinese herbal medicines (CHMs) and the risk of mortality in patients with chronic kidney disease (CKD).DesignNationwide population-based follow-up study.SettingLongitudinal health insurance database sampled from the Taiwan National Health Insurance Research Database.ParticipantsA total of 47 876 patients with CKD were identified. Participants who had ever used AA-containing CHMs, had cancer or HIV prior to the diagnosis of CKD, died within the first month of CKD diagnosis and who were not Taiwanese citizens were excluded. A total of 13 864 participants were eligible for final analysis.Primary and secondary outcome measuresAll-cause mortality among patients with CKD between 2000 and 2008.ResultsAfter controlling for potential confounders, we found that participants who started to receive non-AA prescribed CHMs after the diagnosis of CKD had a lower risk of mortality as compared with non-users of non-AA prescribed CHMs (adjusted HR (aHR) 0.6; 95% CI 0.4 to 0.7, p<0.001). Moreover, participants who had used non-AA prescribed CHMs prior to and after the diagnosis of CKD also had a lower risk of mortality than non-users (aHR 0.6; 95% CI 0.5 to 0.8, p<0.001). In subgroup analyses, we found that such an inverse association was present only among patients who were not eligible to receive erythropoietin therapy (ie, serum creatinine ≦6 mg/dL and/or haematocrit value ≧28%).ConclusionsPatients who received non-AA prescribed CHMs after the diagnosis of CKD, yet before the start of erythropoietin therapy had a lower risk of mortality than those who did not.
Should patients with acute coronary disease be stratified for management according to their risk? Derivation, external validation and outcomes using the updated GRACE risk score
Authors: Fox Keith A A , FitzGerald Gordon , Puymirat Etienne , Huang Wei , Carruthers Kathryn , Simon Tabassome , Coste Pierre , Monsegu Jacques , Gabriel Steg Philippe , Danchin Nicolas , Anderson Fred 
Published: February 2014

ObjectivesRisk scores are recommended in guidelines to facilitate the management of patients who present with acute coronary syndromes (ACS). Internationally, such scores are not systematically used because they are not easy to apply and some risk indicators are not available at first presentation. We aimed to derive and externally validate a more accurate version of the Global Registry of Acute Coronary Events (GRACE) risk score for predicting the risk of death or death/myocardial infarction (MI) both acutely and over the longer term. The risk score was designed to be suitable for acute and emergency clinical settings and usable in electronic devices.Design and settingThe GRACE risk score (2.0) was derived in 32 037 patients from the GRACE registry (14 countries, 94 hospitals) and validated externally in the French registry of Acute ST-elevation and non-ST-elevation MI (FAST-MI) 2005.ParticipantsPatients presenting with ST-elevation and non-ST elevation ACS and with long-term outcomes.Outcome measuresThe GRACE Score (2.0) predicts the risk of short-term and long-term mortality, and death/MI, overall and in hospital survivors.ResultsFor key independent risk predictors of death (1 year), non-linear associations (vs linear) were found for age (p<0.0005), systolic blood pressure (p<0.0001), pulse (p<0.0001) and creatinine (p<0.0001). By employing non-linear algorithms, there was improved model discrimination, validated externally. Using the FAST-MI 2005 cohort, the c indices for death exceeded 0.82 for the overall population at 1 year and also at 3 years. Discrimination for death or MI was slightly lower than for death alone (c=0.78). Similar results were obtained for hospital survivors, and with substitutions for creatinine and Killip class, the model performed nearly as well.ConclusionsThe updated GRACE risk score has better discrimination and is easier to use than the previous score based on linear associations. GRACE Risk (2.0) performed equally well acutely and over the longer term and can be used in a variety of clinical settings to aid management decisions.