bluuebunny/crossref_metadata_2025_split huggingface dataset:
cis
-Acting Elements That Control Expression of the Master Virulence Regulatory Gene
atxA
in Bacillus anthracis
Authors: Dale Jennifer L. , Raynor Malik J. , Dwivedi Prabhat , Koehler Theresa M. 
Published: May 2012

ABSTRACT

Transcription of the
Bacillus anthracis
structural genes for the anthrax toxin proteins and biosynthetic operon for capsule is positively regulated by AtxA, a transcription regulator with unique properties. Consistent with the role of
atxA
in virulence factor expression, a
B. anthracis atxA
-null mutant is avirulent in a murine model for anthrax. In culture, multiple signals impact
atxA
transcript levels, and the timing and steady-state level of
atxA
expression are critical for optimal toxin and capsule synthesis. Despite the apparent complex control of
atxA
transcription, only one
trans
-acting protein, the transition state regulator AbrB, has been demonstrated to interact directly with the
atxA
promoter. Here we employ 5′ and 3′ deletion analysis and site-directed mutagenesis of the
atxA
control region to demonstrate that
atxA
transcription from the major start site P1 is dependent upon a consensus sequence for the housekeeping sigma factor SigA and an A+T-rich upstream element for RNA polymerase. We also show that an additional
trans
-acting protein(s) binds specifically to
atxA
promoter sequences located between −13 and +36 relative to P1 and negatively impacts transcription. Deletion of this region increases promoter activity up to 15-fold. Site-directed mutagenesis of a 9-bp palindromic sequence within the region prevents binding of the
trans
-acting protein(s), increasing promoter activity 7-fold and resulting in a corresponding increase in AtxA and anthrax toxin production. Notably, an
atxA
promoter mutant that produced elevated levels of AtxA and toxin proteins during culture was unaffected for virulence in a murine model for anthrax.
Characterization of the P
IB
-Type ATPases Present in Thermus thermophilus
Authors: Schurig-Briccio Lici A. , Gennis Robert B. 
Published: May 2012

ABSTRACT

P
IB
-type ATPases transport heavy metals (Cu
2+
, Cu
+
, Ag
+
, Zn
2+
, Cd
2+
, Co
2+
) across biomembranes, playing a key role in homeostasis and in the mechanisms of biotolerance of these metals. Three genes coding for putative P
IB
-type ATPases are present in the genome of
Thermus thermophilus
(HB8 and HB27): the TTC1358, TTC1371, and TTC0354 genes; these genes are annotated, respectively, as two copper transporter (CopA and CopB) genes and a zinc-cadmium transporter (Zn
2+
/Cd
2+
-ATPase) gene. We cloned and expressed the three proteins with 8His tags using a
T. thermophilus
expression system. After purification, each of the proteins was shown to have phosphodiesterase activity at 65°C with ATP and
p
-nitrophenyl phosphate (
p
NPP) as substrates. CopA was found to have greater activity in the presence of Cu
+
, while CopB was found to have greater activity in the presence of Cu
2+
. The putative Zn
2+
/Cd
2+
-ATPase was truncated at the N terminus and was, surprisingly, activated
in vitro
by copper but not by zinc or cadmium. When expressed in
Escherichia coli
, however, the putative Zn
2+
/Cd
2+
-ATPase could be isolated as a full-length protein and the ATPase activity was increased by the addition of Zn
2+
and Cd
2+
as well as by Cu
+
. Mutant strains in which each of the three P-type ATPases was deleted singly were constructed. In each case, the deletion increased the sensitivity of the strain to growth in the presence of copper in the medium, indicating that each of the three can pump copper out of the cells and play a role in copper detoxification.
Pathway and Enzyme Redundancy in Putrescine Catabolism in Escherichia coli
Authors: Schneider Barbara L. , Reitzer Larry 
Published: May 2012

ABSTRACT

Putrescine as the sole carbon source requires a novel catabolic pathway with glutamylated intermediates. Nitrogen limitation does not induce genes of this glutamylated putrescine (GP) pathway but instead induces genes for a putrescine catabolic pathway that starts with a transaminase-dependent deamination. We determined pathway utilization with putrescine as the sole nitrogen source by examining mutants with defects in both pathways. Blocks in both the GP and transaminase pathways were required to prevent growth with putrescine as the sole nitrogen source. Genetic and biochemical analyses showed redundant enzymes for γ-aminobutyraldehyde dehydrogenase (PatD/YdcW and PuuC), γ-aminobutyrate transaminase (GabT and PuuE), and succinic semialdehyde dehydrogenase (GabD and PuuC). PuuC is a nonspecific aldehyde dehydrogenase that oxidizes all the aldehydes in putrescine catabolism. A
puuP
mutant failed to use putrescine as the nitrogen source, which implies one major transporter for putrescine as the sole nitrogen source. Analysis of regulation of the GP pathway shows induction by putrescine and not by a product of putrescine catabolism and shows that putrescine accumulates in
puuA
,
puuB
, and
puuC
mutants but not in any other mutant. We conclude that two independent sets of enzymes can completely degrade putrescine to succinate and that their relative importance depends on the environment.
FdhTU-Modulated Formate Dehydrogenase Expression and Electron Donor Availability Enhance Recovery ofCampylobacter jejunifollowing Host Cell Infection
Authors: Pryjma Mark , Apel Dmitry , Huynh Steven , Parker Craig T. , Gaynor Erin C. 
Published: May 2012

ABSTRACTCampylobacter jejuniis a food-borne bacterial pathogen that colonizes the intestinal tract and causes severe gastroenteritis. Interaction with host epithelial cells is thought to enhance severity of disease, and the ability ofC. jejunito modulate its metabolism in differentin vivoand environmental niches contributes to its success as a pathogen. AC. jejunioperon comprising two genes that we designatedfdhT(CJJ81176_1492) andfdhU(CJJ81176_1493) is conserved in many bacterial species. Deletion offdhTorfdhUinC. jejuniresulted in apparent defects in adherence and/or invasion of Caco-2 epithelial cells when assessed by CFU enumeration on standard Mueller-Hinton agar. However, fluorescence microscopy indicated that each mutant invaded cells at wild-type levels, instead suggesting roles for FdhTU in either intracellular survival or postinvasion recovery. The loss offdhUcaused reduced mRNA levels of formate dehydrogenase (FDH) genes and a severe defect in FDH activity. Cell infection phenotypes of a mutant deleted for the FdhA subunit of FDH and an ΔfdhUΔfdhAdouble mutant were similar to those of a ΔfdhUmutant, which likewise suggested that FdhU and FdhA function in the same pathway. Cell infection assays followed by CFU enumeration on plates supplemented with sodium sulfite abolished the ΔfdhUand ΔfdhAmutant defects and resulted in significantly enhanced recovery of all strains, including wild type, at the invasion and intracellular survival time points. Collectively, our data indicate that FdhTU and FDH are required for optimal recovery following cell infection and suggest thatC. jejunialters its metabolic potential in the intracellular environment.
Growth Phase-Dependent Modulation of Rgg Binding Specificity in Streptococcus pyogenes
Authors: Anbalagan Srivishnupriya , Dmitriev Alexander , McShan W. Michael , Dunman Paul M. , Chaussee Michael S. 
Published: May 2012

ABSTRACT

Streptococcus pyogenes
Rgg is a transcriptional regulator that interacts with the cofactor LacD.1 to control growth phase-dependent expression of genes, including
speB
, which encodes a secreted cysteine protease. LacD.1 is thought to interact with Rgg when glycolytic intermediates are abundant in a manner that prevents Rgg-mediated activation of
speB
expression via binding to the promoter region. When the intermediates diminish, LacD.1 dissociates from Rgg and binds to the
speB
promoter to activate expression. The purpose of this study was to determine if Rgg bound to chromatin during the exponential phase of growth and, if so, to identify the binding sites. Rgg bound to 62 chromosomal sites, as determined by chromatin immunoprecipitation coupled with DNA microarrays. Thirty-eight were within noncoding DNA, including sites upstream of the genes encoding the M protein (M49), serum opacity factor (SOF), fibronectin-binding protein (SfbX49), and a prophage-encoded superantigen, SpeH. Each of these sites contained a promoter that was regulated by Rgg, as determined with transcriptional fusion assays. Purified Rgg also bound to the promoter regions of
emm49
,
sof
, and
sfbX49 in vitro
. Results obtained with a
lacD.1
mutant showed that both LacD.1 and Rgg were necessary for the repression of
emm49
,
sof
,
sfbX49
, and
speH
expression. Overall, the results indicated that the DNA binding specificity of Rgg is responsive to environmental changes in a LacD.1-dependent manner and that Rgg and LacD.1 directly control virulence gene expression in the exponential phase of growth.
Illness during the 2010 Super 14 Rugby Union tournament – a prospective study involving 22 676 player days
Authors: Schwellnus Martin , Derman Wayne , Page Tony , Lambert Michael , Readhead Clint , Roberts Craig , Kohler Ryan , Jordaan Esme , Collins Robert , Kara Stephen , Morris Ian , Strauss Org , Webb Sandra 
Published: May 2012

BackgroundIllness accounts for a significant proportion of consultations with a team physician travelling with elite athletes.ObjectiveTo determine the incidence, type, cause and consequences of illness in Rugby Union players participating in a 16-week tournament.Setting8 teams participating in the 2010 Super 14 Rugby tournamentParticipantsA cohort of 259 elite rugby players from eight teams was recruited.AssessmenAll players were followed daily over the 16-week competition period (22 676 player days). Each day, team physicians completed an illness log with 100% compliance. Information included the daily squad size and illness details including system affected, final diagnosis, type and onset of symptoms, training/match days lost and suspected cause.Main outcome measurementIncidence of illness (illness per 1000 player days).ResultsThe incidence of illness in the cohort was 20.7/1000 player days (95% CI 18.5 to 23.1) with the highest incidence of illness in the respiratory system (6.4: 95% CI 5.5 to 7.3), gastrointestinal system (5.6: 95% CI 4.9 to 6.6) and the skin and subcutaneous tissue (4.6; 95% CI 4.0 to 5.4). Infections accounted for 54.5% of all illness and 26.1% of illness resulted in time loss of ≥1 day. In over 50% of illnesses, symptoms were present for ≥1 day before being reported to the team physician.ConclusionInfective illness involving the respiratory tract and gastrointestinal tract together with dermatological illness was common in elite rugby players participating in this international tournament. A delay in reporting of symptoms >24 h could have important clinical implications in player medical care.
The economic benefit of hip replacement: a 5-year follow-up of costs and outcomes in the Exeter Primary Outcomes Study
Authors: Fordham Richard , Skinner Jane , Wang Xia , Nolan John ,   the Exeter Primary Outcome Study Group
Published: May 2012

ObjectivesTo assess changes in quality of life and costs of patients undergoing primary total hip replacement using the Exeter prosthesis compared with a hypothetical ‘no surgery’ group.DesignThe incremental quality of life, quality-adjusted life years (QALYs) and cost of Exeter Primary Outcomes Study patients was compared with hypothetical ‘no surgery’ group over 5 years. Scores from annual SF-36 assessments were converted into utility scores using an established algorithm and the QALY gains calculated from pre-operative baseline scores. Costs included implant costs and length of stay.SettingSecondary care hospitals.ParticipantsPatients receiving a primary Exeter implant enrolled in five of seven Exeter Primary Outcomes Study centres.ResultsOn average, patients gained around 0.8 QALYs over 5 years. Younger and male patients or those with lower body mass index and poorer Oxford Hip Scores were significantly associated with increased QALYs. Treatment costs for a primary episode of care were just over £5000 (95% CI £4588 to £5812) per patient. Compared with ‘no surgery’, the cost per QALY was £7182 (95% CI £6470 to £7678), and this remained stable when key cost parameters were varied. The most likely cost per QALY was between £7058 and £7220. Older patients (age 75+) cost more, mainly due to longer average hospital stays and had a higher cost per QALY, although this remained below £10 000.Conclusions85% of cases had a cost of <£20 000 per QALY (with 70% having a cost per QALY under £10 000) compared with no surgery. Cases would be considered cost-effective under currently accepted thresholds (£25 000–£30 000) compared with ‘no surgery’. However, depending on age and severity, younger patients and more severe patients had below average cost per QALYs. These results help to confirm the long-term benefits and cost-effectiveness of total hip replacement in a wide variety of patients using well-established implant models such as the Exeter. However, further and ongoing economic appraisal of this and other models is required for comparative purposes.
Registration of surgical adverse outcomes: a reliability study in a university hospital
Authors: Ubbink Dirk T , Visser Annelies , Gouma Dirk J , Goslings J Carel 
Published: May 2012

ObjectiveAccurate registration of adverse surgical outcomes is essential to detect areas for improvement of surgical care quality. One reason for inaccurate adverse outcome registration may be the method to collect these outcomes. The authors compared the completeness of the national complication registry database (LHCR) as used in our hospital with relevant information from other available resources.DesignRetrospective reliability analysis.SettingUniversity hospital.ParticipantsFrom the 3252 patients admitted to the surgical wards in 2010, the authors randomly selected a cohort of 180 cases, oversampling those with adverse outcomes. The LHCR contains adverse outcomes as reported during morning hand-offs or in discharge letters. The authors checked if the number and severity of adverse outcomes recorded in the LHCR agreed with those reported in morning hand-offs, discharge letters and medical and nursing files.ResultsIn 135 of 180 patients, all resources could be retrieved completely. Fourteen per cent of the patients with adverse outcomes were not recorded in the LHCR. Missing adverse outcomes were all reversible without the need for (re)operation, for example, postoperative pain, delirium or urinary tract complications. Only 38% of these adverse outcomes were reported in the morning hand-offs and discharge letters but were best reported in the medical and nursing files.ConclusionsRegistration of surgical adverse outcomes appears largely depending on the reliability of the underlying sources. For a more complete adverse outcome registration, the authors advocate a better hand-off and additional consultation of the patient's dossier. This extra effort allows for improvement actions to eventually avoid ‘mild’ adverse outcomes patients perceive as important and undesirable.
Impact of a pharmacist-prepared interim residential care medication administration chart on gaps in continuity of medication management after discharge from hospital to residential care: a prospective pre- and post-intervention study (MedGap Study)
Authors: Elliott Rohan A , Tran Tim , Taylor Simone E , Harvey Penelope A , Belfrage Mary K , Jennings Rhonda J , Marriott Jennifer L 
Published: May 2012

ObjectivesTo test the impact of a hospital pharmacist-prepared interim residential care medication administration chart (IRCMAC) on medication administration errors and use of locum medical services after discharge from hospital to residential care.DesignProspective pre-intervention and post-intervention study.SettingOne major acute care hospital and one subacute aged-care hospital; 128 residential care facilities (RCF) in Victoria, Australia.Participants428 patients (median age 84 years, IQR 79–88) discharged to a RCF from an inpatient ward over two 12-week periods.InterventionSeven-day IRCMAC auto-populated with patient and medication data from the hospitals' pharmacy dispensing software, completed and signed by a hospital pharmacist and sent with the patient to the RCF.Primary and secondary outcome measuresPrimary end points were the proportion of patients with one or more missed or significantly delayed (>50% of prescribed dose interval) medication doses, and the proportion of patients whose RCF medication chart was written by a locum doctor, in the 24 h after discharge. Secondary end points included RCF staff and general practitioners' opinions about the IRCMAC.ResultsThe number of patients who experienced one or more missed or delayed doses fell from 37/202 (18.3%) to 6/226 (2.7%) (difference in percentages 15.6%, 95% CI 9.5% to 21.9%, p<0.001). The number of patients whose RCF medication chart was written by a locum doctor fell from 66/202 (32.7%) to 25/226 (11.1%) (difference in percentages 21.6%, 95% CI 13.5% to 29.7%, p<0.001). For 189/226 (83.6%) discharges, RCF staff reported that the IRCMAC improved continuity of care; 31/35 (88.6%) general practitioners said that the IRCMAC reduced the urgency for them to attend the RCF and 35/35 (100%) said that IRCMACs should be provided for all patients discharged to a RCF.ConclusionsA hospital pharmacist-prepared IRCMAC significantly reduced medication errors and use of locum medical services after discharge from hospital to residential care.
Social differences in lung cancer management and survival in South East England: a cohort study
Authors: Berglund Anders , Lambe Mats , Lüchtenborg Margreet , Linklater Karen , Peake Michael D , Holmberg Lars , Møller Henrik 
Published: May 2012

ObjectiveTo examine possible social variations in lung cancer survival and assess if any such gradients can be attributed to social differences in comorbidity, stage at diagnosis or treatment.DesignPopulation-based cohort identified in the Thames Cancer Registry.SettingSouth East England.Participants15 582 lung cancer patients diagnosed between 2006 and 2008.Main outcome measuresStage at diagnosis, surgery, radiotherapy, chemotherapy and survival.ResultsThe likelihood of being diagnosed as having early-stage disease did not vary by socioeconomic quintiles (p=0.58). In early-stage non-small-cell lung cancer, the likelihood of undergoing surgery was lowest in the most deprived group. There were no socioeconomic differences in the likelihood of receiving radiotherapy in stage III disease, while in advanced disease and in small-cell lung cancer, receipt of chemotherapy differed over socioeconomic quintiles (p<0.01). In early-stage disease and following adjustment for confounders, the HR between the most deprived and the most affluent group was 1.24 (95% CI 0.98 to 1.56). Corresponding estimates in stage III and advanced disease or small-cell lung cancer were 1.16 (95% CI 1.01 to 1.34) and 1.12 (95% CI 1.05 to 1.20), respectively. In early-stage disease, the crude HR between the most deprived and the most affluent group was approximately 1.4 and constant through follow-up, while in patients with advanced disease or small-cell lung cancer, no difference was detectable after 3 months.ConclusionWe observed socioeconomic variations in management and survival in patients diagnosed as having lung cancer in South East England between 2006 and 2008, differences which could not fully be explained by social differences in stage at diagnosis, co-morbidity and treatment. The survival observed in the most affluent group should set the target for what is achievable for all lung cancer patients, managed in the same healthcare system.
Detailed protocol for the lifestyle intervention in the BeWEL randomised controlled trial of weight loss in adults who have had a colorectal adenoma
Authors: Caswell Stephen , Craigie Angela M , Wardle Jane , Stead Martine , Anderson Annie 
Published: May 2012

IntroductionThe BeWEL study is aimed at assessing the impact of a personalised lifestyle programme on body weight in people at risk of developing colorectal adenomas. The study is a two-arm multicentre randomised controlled trial comparing the BeWEL lifestyle programme against usual care. Over 12 months, 316 people who have had a colorectal adenoma removed through the national screening programme will be randomised to provide 80% power to detect a weight loss (primary outcome) of 7% over 12 months.MethodsThe 12-month intervention will be delivered by lifestyle counsellors via three face-to-face visits followed by nine monthly telephone support calls. Consultant endorsement for the study will be stressed. An individualised caloric prescription based on estimates for weight maintenance −600 kcal will be calculated. Motivational interviewing techniques will be used to identify personal motivations for weight change and ways to improve perceived self-efficacy. The programme will utilise personalised diet and physical activity data from baseline measures to set behavioural goals. A range of behavioural strategies will be employed to support lifestyle change including goal setting, identifying specific implementation intentions, self-monitoring and feedback. Emphasis will be placed on self-monitoring body weight, and weighing scales will be provided. Programme acceptability will be explored postintervention with indepth interviews. Compliance and impact will be assessed by baseline and follow-up measures of diet by self-report, activity by accelerometry and anthropometry.Ethics and disseminationEthical approval has been obtained from the Tayside Committee on Medical Research Ethics. Dissemination of results will focus on publications in peer-reviewed journals, presentations at national/international cancer meetings and NHS groups. In addition, the work will be communicated to the public through forums such at The Scottish Cancer Prevention Network (http://www.cancerpreventionscotland.co.uk/). The trial is registered with Current Controlled Trials (International Standard Randomised Controlled Trials No:ISRCTN53033856).
Implementation of a novel communication tool and its effect on patient comprehension of care and satisfaction
Authors: Simmons Stefanie Anne , Sharp Brian , Fowler Jennifer , Singal Bonita 
Published: May 2012

BackgroundEmergency department (ED) communication has been demonstrated as requiring improvement and ED patients have repeatedly demonstrated poor comprehension of the care they receive. Through patient focus groups, the authors developed a novel tool designed to improve communication and patient comprehension.Study designThis is a prospective, randomised controlled clinical trial to test the efficacy of a novel, patient-centred communication tool. Patients in a small community hospital ED were randomised to receive the instrument, which was utilised by the entire ED care team and served as a checklist or guide to the patients' ED stay. At the end of the ED stay, patients completed a survey of their comprehension of the care and a communication assessment tool-team survey (a validated instrument to assess satisfaction with communication). Three blinded chart reviewers scored patients' comprehension of their ED care as concordant, partially concordant or discordant with charted care. The authors tested whether there was a difference in satisfaction using a two-sample t test and a difference in comprehension using ordinal logistic regression analysis.Results146 patients were enrolled in the study with 72 randomised to receive the communication instrument. There was no significant difference between groups in comprehension (OR=0.65, 95% CI 0.34 to 1.23, p=0.18) or communication assessment tool-team scores (difference=0.2, 95% CI: −3.4 to 3.8, p=0.91).ConclusionsUsing their novel communication tool, the authors were not able to show a statistically significant improvement in either comprehension or satisfaction, though a tendency towards improved comprehension was seen.