bluuebunny/crossref_metadata_2025_split huggingface dataset:
AccD6, a Key Carboxyltransferase Essential for Mycolic Acid Synthesis in Mycobacterium tuberculosis, Is Dispensable in a Nonpathogenic Strain
Authors: Pawelczyk Jakub , Brzostek Anna , Kremer Laurent , Dziadek Bozena , Rumijowska-Galewicz Anna , Fiolka Marta , Dziadek Jaroslaw 
Published: October 2011

ABSTRACTAcetyl coenzyme A carboxylase (ACC) is a key enzyme providing a substrate for mycolic acid biosynthesis. Althoughin vitrostudies have demonstrated that the protein encoded byaccD6(Rv2247) may be a functional carboxyltransferase subunit of ACC inMycobacterium tuberculosis, thein vivofunction and regulation ofaccD6in slow- and fast-growing mycobacteria remain elusive. Here, directed mutagenesis demonstrated that althoughaccD6is essential forM. tuberculosis, it can be deleted inMycobacterium smegmatiswithout affecting its cell envelope integrity. Moreover, we showed that although it is part of the type II fatty acid synthase operon, theaccD6gene ofM. tuberculosis, but not that ofM. smegmatis, possesses its own additional promoter (Pacc). The expression level ofaccD6Mtbplaced only under the control of Paccis 10-fold lower than that in wild-typeM. tuberculosisbut is sufficient to sustain cell viability. Importantly, this limited expression level affects growth, mycolic acid content, and cell morphology. These results provide the firstin vivoevidence for AccD6 as a key player in the mycolate biosynthesis ofM. tuberculosis, implicating AccD6 as the essential ACC subunit in pathogenic mycobacteria and an excellent target for new antitubercular compounds. Our findings also highlight important differences in the mechanism of acetyl carboxylation between pathogenic and nonpathogenic mycobacterial species.
Hydrogen Peroxide-Dependent DNA Release and Transfer of Antibiotic Resistance Genes in Streptococcus gordonii
Authors: Itzek Andreas , Zheng Lanyan , Chen Zhiyun , Merritt Justin , Kreth Jens 
Published: October 2011

ABSTRACTCertain oral streptococci produce H2O2under aerobic growth conditions to inhibit competing species likeStreptococcus mutans. Additionally, H2O2production causes the release of extracellular DNA (eDNA). eDNA can participate in several important functions: biofilm formation and cell-cell aggregation are supported by eDNA, while eDNA can serve as a nutrient and as an antimicrobial agent by chelating essential cations. eDNA contains DNA fragments of a size that has the potential to transfer genomic information. By usingStreptococcus gordoniias a model organism for streptococcal H2O2production, H2O2-dependent eDNA release was further investigated. Under defined growth conditions, the eDNA release process was shown to be entirely dependent on H2O2. Chromosomal DNA damage seems to be the intrinsic signal for the release, although only actively growing cells were proficient eDNA donors. Interestingly, the process of eDNA production was found to be coupled with the induction of theS. gordoniinatural competence system. Consequently, the production of H2O2triggered the transfer of antibiotic resistance genes. These results suggest that H2O2is potentially much more than a simple toxic metabolic by-product; rather, its production could serve as an important environmental signal that facilitates species evolution by transfer of genetic information and an increase in the mutation rate.
Regulation of the Competence Pathway as a Novel Role Associated with a Streptococcal Bacteriocin
Authors: Dufour Delphine , Cordova Martha , Cvitkovitch Dennis G. , Lévesque Céline M. 
Published: October 2011

ABSTRACT

The oral biofilm organism
Streptococcus mutans
must face numerous environmental stresses to survive in its natural habitat. Under specific stresses,
S. mutans
expresses the competence-stimulating peptide (CSP) pheromone known to induce autolysis and facilitate the uptake and incorporation of exogenous DNA, a process called DNA transformation. We have previously demonstrated that the CSP-induced CipB bacteriocin (mutacin V) is a major factor involved in both cellular processes. Our objective in this work was to characterize the role of CipB bacteriocin during DNA transformation. Although other bacteriocin mutants were impaired in their ability to acquire DNA under CSP-induced conditions, the Δ
cipB
mutant was the only mutant showing a sharp decrease in transformation efficiency. The autolysis function of CipB bacteriocin does not participate in the DNA transformation process, as factors released via lysis of a subpopulation of cells did not contribute to the development of genetic competence in the surviving population. Moreover, CipB does not seem to participate in membrane depolarization to assist passage of DNA. Microarray-based expression profiling showed that under CSP-induced conditions, CipB regulated ∼130 genes, among which are the
comDE
locus and
comR
and
comX
genes, encoding critical factors that influence competency development in
S. mutans
. We also discovered that the CipI protein conferring immunity to CipB-induced autolysis also prevented the transcriptional regulatory activity of CipB. Our data suggest that besides its role in cell lysis, the
S. mutans
CipB bacteriocin also functions as a peptide regulator for the transcriptional control of the competence regulon.
Production of Multiple Bacteriocins from a Single Locus by Gastrointestinal Strains of Lactobacillus salivarius
Authors: O'Shea Eileen F. , O'Connor Paula M. , Raftis Emma J. , O'Toole Paul W. , Stanton Catherine , Cotter Paul D. , Ross R. Paul , Hill Colin 
Published: October 2011

ABSTRACT

Bacteriocins produced by
Lactobacillus salivarius
isolates derived from a gastrointestinal origin have previously demonstrated efficacy for
in vivo
protection against
Listeria monocytogenes
infection. In this study, comparative genomic analysis was employed to investigate the intraspecies diversity of seven
L. salivarius
isolates of human and porcine intestinal origin, based on the genome of the well-characterized bacteriocin-producing strain
L. salivarius
UCC118. This revealed a highly conserved megaplasmid-borne gene cluster in these strains involved in the regulation and secretion of two-component class IIb bacteriocins. However, considerable intraspecific variation was observed in the structural genes encoding the bacteriocin peptides. They ranged from close relatives of abp118, such as salivaricin P, which differs by 2 amino acids, to completely novel bacteriocins, such as salivaricin T, which is characterized in this study. Salivaricin T inhibits closely related lactobacilli and bears little homology to previously characterized salivaricins. Interestingly, the two peptides responsible for salivaricin T activity, SalTα and SalTβ, share considerable identity with the component peptides of thermophilin 13, a bacteriocin produced by
Streptococcus thermophilus
. Furthermore, the salivaricin locus of strain DPC6488 also encodes an additional novel one-component class IId anti-listerial bacteriocin, salivaricin L. These findings suggest a high level of redundancy in the bacteriocins that can be produced by intestinal
L. salivarius
isolates using the same enzymatic production and export machinery. Such diversity may contribute to their ability to dominate and compete within the complex microbiota of the mammalian gut.
Covered stents safely utilized to prevent catastrophic hemorrhage in patients with advanced head and neck malignancy
Authors: Miller Todd , Burns Judah , Farinhas Joaquim , Pasquale David , Haboosheh Amit , Bello Jacqueline A , Brook Allan 
Published: October 2011

PurposeThe purpose of this study was to review the use of covered stents in patients with squamous cell carcinoma of the head and neck threatening bilateral neurovascular structures.MethodsThe radiology information system was searched for all patients with bilateral head and neck carcinoma treated with covered stents in the carotid vasculature from 2006 through 2009. Five patients (one woman) of mean age 60.5 years (range 45–69) were identified. All had carotid blowout syndrome after treatment for primary squamous cell carcinoma of the head and neck with subsequent tumor recurrence or metastases immediately threatening bilateral carotid vasculature. Covered stents were placed. Long-term follow-up included clinical progress, verification of stent patency and detection of tumor progression via ultrasound or contrast-enhanced CT after the first month and then every 3–6 months. All patients were maintained on antiplatelet medication after treatment.ResultsCovered stents were safely deployed in all patients. Mean survival was 5 months with one outlier surviving for 3 years. There were no subsequent uncontrollable hemorrhages.ConclusionThe use of covered stents for avoidance of catastrophic hemorrhage following treatment in patients with head and neck tumors with bilaterally threatened carotid arteries was successful.
Use of web based systems to support postgraduate medical education
Authors: Tochel C , Beggs K , Haig A , Roberts J , Scott H , Walker K , Watson M 
Published: October 2011

ABSTRACT

Background
To meet the demands of delivering the Foundation programme across a geographically diverse country, two web based systems (ePortfolio and eLearning) were developed to promote accessibility to training material and assessment tools on standardised platforms. This study evaluated the use of both tools throughout an entire academic year.

Methods
All Scottish Foundation trainees' online learning and assessment data in 2007/08 were analysed, providing a national breakdown of post specialty, completion rates of mandatory assessments (including summary analysis of anonymised scores), and trainees' use of non-mandatory learning tools. Independent verification of competence data was sought from Deaneries.

Results
There were high levels of engagement with both the ePortfolio (75–97% assessment completion) and eLearning systems (89–98% induction course completion), and the majority of trainees completed all required elements. There was extensive use of ePortfolio beyond mandatory levels for recording of learning events, including almost 20 000 personal learning records submitted by second year trainees. There was evidence that ePortfolio was used to record achievement of clinical competence rather than to track improvements towards competence (median workplace based assessment scores were ‘high’ or ‘very high’). Online learning modules received positive feedback and its flexible format suited the trainees' working environment. External verification of formal assessment data revealed good correlation with locally stored outcomes, both indicating approximately 99% programme completion rates.

Conclusions
Core components of the Foundation programme have been delivered successfully to thousands of trainees across Scotland using web based systems to deliver and support education and assessment. There is great potential for further exploration of this carefully managed, rich dataset at individual, regional, and national levels to inform the future of medical education.
Effects of changing work patterns on general surgical training over the last decade
Authors: Blencowe N S , Parsons B A , Hollowood A D 
Published: October 2011

ABSTRACT

Background
There is concern across all medical specialties that shift patterns and reduced working hours are detrimental to training, and that craft specialties have been most affected. This study aimed to examine the effects of these changes to training on the quantity of operating performed by surgical trainees in a UK teaching hospital.

Methods
This retrospective study of prospectively collected computerised theatre data examined elective and emergency general surgical operations performed over four time periods: 1996 (Calman), 2001 (New Deal), 2004 and 2009 (European Working Time Directive). Procedures were analysed according to grade of surgeon and time of day.

Results
In 1996, most appendicectomies (72.2%) were performed by senior house officers (SHOs), compared with 3.8% in 2009. By 2009, SHOs did not perform any emergency procedures other than abscess drainage and appendicectomy. The proportion of emergency operating performed by specialist registrar (SpRs) has remained constant, but elective operating has reduced from 34.6% (1996) to 15.7% (2009). Supervision of both SHOs and SpRs has increased between 1996 and 2009 in both elective and emergency work.

Conclusions
The proportion of operating performed by SpRs and SHOs has fallen over the last decade, coinciding with implementation of structural changes to training, the advent of minimally invasive techniques, and the drive for a consultant led health service. Trainees may therefore require increased supervision as well as protected theatre sessions to balance operative training with ward based duties. Education must be integrated into working practice in order for trainees to achieve expected competencies and ultimately produce adequately experienced consultants.
Improved measures of racial mixing among men who have sex with men using Newman's assortativity coefficient
Authors: Bohl Daniel D , McFarland Willi , Raymond H Fisher 
Published: October 2011

ObjectiveTo measure sexual mixing among racial groups of men who have sex with men (MSM).MethodsThe authors explore its potential impacts, making two methodological advancements over previous work. First, the authors pioneer the use of Newman's assortativity coefficient to characterise mixing among MSM. Second, the authors examine mixing at the level of primary ties and at the level of secondary ties.ResultsResults from the 1142-participant sample suggest that MSM are highly assortative by all races at the secondary level.ConclusionsNetworks of MSM may be more tightly contracted around racial groupings than previously supposed. These groupings may lead to increased HIV transmission in certain racial groups.
Weight Cycling and Cancer: Weighing the Evidence of Intermittent Caloric Restriction and Cancer Risk
Authors: Thompson Henry J. , McTiernan Anne 
Published: October 2011

Abstract
Overweight and obese individuals frequently restrict caloric intake to lose weight. The resultant weight loss, however, typically is followed by an equal or greater weight gain, a phenomenon called weight cycling. Most attention to weight cycling has focused on identifying its detrimental effects, but preclinical experiments indicating that intermittent caloric restriction or fasting can reduce cancer risk have raised interest in potential benefits of weight cycling. Although hypothesized adverse effects of weight cycling on energy metabolism remain largely unsubstantiated, there is also a lack of epidemiologic evidence that intentional weight loss followed by regain of weight affects chronic-disease risk. In the limited studies of weight cycling and cancer, no independent effect on postmenopausal breast cancer but a modest enhancement of risk for renal cell carcinoma, endometrial cancer, and non-Hodgkin's lymphoma have been reported. An effect of either intermittent caloric restriction or fasting in protecting against cancer is not supported by the majority of rodent carcinogenesis experiments. Collectively, the data argue against weight cycling and indicate that the objective of energy balance–based approaches to reduce cancer risk should be to strive to prevent adult weight gain and maintain body weight within the normal range defined by body mass index. Cancer Prev Res; 4(11); 1736–42. ©2011 AACR.
Inflammatory Marker Changes in a Yearlong Randomized Exercise Intervention Trial among Postmenopausal Women
Authors: Friedenreich Christine M. , Neilson Heather K. , Woolcott Christy G. , Wang Qinggang , Stanczyk Frank Z. , McTiernan Anne , Jones Charlotte A. , Irwin Melinda L. , Yasui Yutaka , Courneya Kerry S. 
Published: October 2011

Abstract
Chronic low-grade inflammation is a possible risk factor for cancer that may be modifiable with long-term exercise. Very few randomized controlled trials (RCT) have studied the isolated effects of exercise on low-grade inflammation exclusively in postmenopausal women. The Alberta Physical Activity and Breast Cancer Prevention Trial, a 2-armed RCT in healthy postmenopausal women, examined how 1 year of moderate to vigorous aerobic exercise, compared with usual inactivity, influenced circulating inflammatory markers. Baseline, 6-month, and 12-month serum was analyzed by direct chemiluminescent immunoassays to measure high sensitivity C-reactive protein (CRP) and ELISAs to measure interleukin 6 (IL-6) and TNF-α. Intention to treat analyses were conducted with linear mixed models. Statistically significant differences in CRP were observed over 12 months for exercisers versus controls (treatment effect ratio = 0.87, 95% CI = 0.79–0.96, P = 0.005), but not in IL-6 or TNF-α. A statistically significant trend (Ptrend = 0.021) of decreasing CRP with increasing exercise adherence and stronger intervention effects on CRP in women with higher baseline physical fitness (Pheterogeneity = 0.040) was found. The intervention effect on CRP became statistically nonsignificant with adjustment for dietary fiber intake change and seemed to be mediated by fat loss. Low-grade inflammation may be lowered with exercise, but confounding by dietary intake occurred and should be considered in future studies. Further trials are needed to corroborate our findings about the optimal dose of exercise required to lower CRP levels and effect modification of CRP changes by levels of body fatness and fitness. Cancer Prev Res; 5(1); 98–108. ©2011 AACR.
Transcoronary Ethanol Ablation for Recurrent Ventricular Tachycardia After Failed Catheter Ablation
Authors: Tokuda Michifumi , Sobieszczyk Piotr , Eisenhauer Andrew C. , Kojodjojo Pipin , Inada Keiichi , Koplan Bruce A. , Michaud Gregory F. , John Roy M. , Epstein Laurence M. , Sacher Frédéric , Stevenson William G. , Tedrow Usha B. 
Published: October 2011

Background—
Despite substantial progress, radiofrequency catheter ablation (RFCA) fails in some patients. After encouraging results with transcoronary ethanol ablation (TCEA), we began offering TCEA routinely when endocardial and epicardial RFCA failed or a deep intramural substrate was likely.

Methods and Results—
Among 274 consecutive patients who underwent 408 ventricular tachycardia (VT) ablation procedures, 27 patients (21 men; age, 63±13 years; left ventricular ejection fraction, 30±11%; ischemic cardiomyopathy, 14) had 29 TCEA procedures attempted. In 5 patients, TCEA was abandoned because of unfavorable anatomy. In 22 patients, a mean of 1.3±0.6 arteries (range, 1–3 arteries) were targeted for TCEA. After ablation, the targeted VT was no longer inducible in 18 of 22 (82%) patients. Complete heart block occurred in 5 patients, and 3 patients with advanced heart failure died within 30 days of the procedure. After the last TCEA procedure, a VT recurred in 64% of patients, and overall, 32% of patients died. Of 11 patients with prior VT storm, 9 were free of VT storm. At repeat study in 8 patients who had a recurrence, 7 had a new QRS morphology of VT originating from the same general substrate region as the prior VT.

Conclusions—
In patients with difficult-to-control VT in whom RFCA fails, TCEA prevents all VT recurrences in 36% and improves arrhythmia control in an additional 27%. Inadequate target vessels, collaterals, and recurrence of modified VTs limit efficacy, but TCEA continues to play an important role for difficult VTs in these high-risk patients.
Genomic Risk Variants at 1p13.3, 1q41, and 3q22.3 Are Associated With Subsequent Cardiovascular Outcomes in Healthy Controls and in Established Coronary Artery Disease
Authors: Ellis Katrina L. , Frampton Chris M. , Pilbrow Anna P. , Troughton Richard W. , Doughty Rob N. , Whalley Gillian A. , Ellis Chris J. , Skelton Lorraine , Thomson Judith , Yandle Tim G. , Richards A. Mark , Cameron Vicky A. 
Published: October 2011

Background—
Genome-wide association studies have identified gene variants associated with coronary artery disease risk; however, whether they affect disease progression is largely unknown. This study investigated associations between polymorphisms at 1p13.3 (rs599839), 1q41 (rs17465637), and 3q22.3 (rs9818870) and cardiovascular outcomes in healthy volunteers and in patients with established heart disease.

Methods and Results—

Canterbury Healthy Volunteer study (HV) (n=1649), Coronary Disease Cohort Study (CDCS) (n=1797), and Post-Myocardial Infarction study (PMI) (n=906) participants (New Zealand), were genotyped for rs599839, rs9818870, and rs17465637. Associations between genotype and anthropometric characteristics, neurohormonal analysis, echocardiography, and clinical outcomes over medium-long-term follow-up (median HV, 5.9 years; CDCS, 3.7 years; PMI, 11.3 years) were tested. At 1p13.3, HV and CDCS participants carrying 1 or more rs599839 G allele had a lower prevalence of dyslipidemia (
P
≤0.005) or lower levels of low-density lipoprotein (
P
=0.031) and total (
P
=0.004) cholesterol and/or less history of myocardial infarction (
P
≤0.04) compared with AA participants. Moreover, CDCS and PMI AG/GG participants had better cardiac function as indicated by echocardiography (
P
≤0.026), and fewer CDCS AG/GG participants were readmitted for a non-ST-segment elevation MI (
P
=0.012) during follow-up. The polymorphism at 1q41 (rs17465637) was associated with better cardiovascular outcomes in the HV (
P
=0.028) and PMI (
P
=0.008) cohorts, and 3q22.3 (rs9818870) was a predictor of death/admission in the HV cohort (
P
=0.045).

Conclusions—
These data suggest that coronary artery disease genomic risk variants at 1p13.3 and 1q41 are associated with subsequent clinical outcome in heart patients and confirm rs9818870 at 3q22.3 as a predictor of cardiovascular risk in individuals free of overt heart disease.
The Growth of Unproductive Activities, the Rate of Profit, and the Phase-Change of the U.S. Economy
Authors: Paitaridis Dimitris , Tsoulfidis Lefteris 
Published: October 2011

This paper by using the categories of productive and unproductive labor and by extending and further elaborating the data series utilized in Shaikh and Tonak (1994) reveals a sharp expansion of the unproductive activities in the U.S. economy during the period 1964-2007. The combination of growing productivity and the stagnant or even falling real wages of productive workers increased the rate of surplus value in the recent decades to unprecedented highs. As a consequence, the general rate of profit from the early 1980s onwards was also rising until the last years of our analysis; meanwhile the net rate of profit remained at levels much lower than those of the 1960s and the slightly rising trend during the post-1980s has been already reversed. The patterns of these crucial variables reveal startling similarities with the onset of the slowdown that started in the mid- to late 1960s. JEL classification: B5, E1, O51