bluuebunny/crossref_metadata_2025_split huggingface dataset:
Substitutions in the BamA β-Barrel Domain Overcome the Conditional Lethal Phenotype of a Δ
bamB
Δ
bamE
Strain of Escherichia coli
Authors: Tellez Rene , Misra Rajeev 
Published: October 2011

ABSTRACT

BamA interacts with the BamBCDE lipoproteins, and together they constitute the essential β-barrel assembly machine (BAM) of
Escherichia coli
. The simultaneous absence of BamB and BamE confers a conditional lethal phenotype and a severe β-barrel outer membrane protein (OMP) biogenesis defect. Without BamB and BamE, wild-type BamA levels are significantly reduced, and the folding of the BamA β-barrel, as assessed by the heat-modifiability assay, is drastically compromised. Single-amino-acid substitutions in the β-barrel domain of BamA improve both bacterial growth and OMP biogenesis in a
bamB bamE
mutant and restore BamA levels close to the BamB
+
BamE
+
level. The substitutions alter BamA β-barrel folding, and folding in the mutants becomes independent of BamB and BamE. Remarkably, BamA β-barrel alterations also improve OMP biogenesis in cells lacking the major periplasmic chaperone, SurA, which, together with BamB, is thought to facilitate the transfer of partially folded OMPs to the soluble POTRA (polypeptide-transport-associated) domain of BamA. Unlike the
bamB bamE
mutant background, the absence of BamB or SurA does not affect BamA β-barrel folding. Thus, substitutions in the outer membrane-embedded BamA β-barrel domain overcome OMP biogenesis defects that occur at the POTRA domain of BamA in the periplasm. Based on the structure of FhaC, the altered BamA residues are predicted to lie on a highly conserved loop that folds inside the β-barrel and in regions pointing outside the β-barrel, suggesting that they influence BamA function by both direct and indirect mechanisms.
Comprehensive Transcriptome Analysis of the Periodontopathogenic Bacterium Porphyromonas gingivalis W83
Authors: Høvik Hedda , Yu Wen-Han , Olsen Ingar , Chen Tsute 
Published: October 2011

ABSTRACT

High-density tiling microarray and RNA sequencing technologies were used to analyze the transcriptome of the periodontopathogenic bacterium
Porphyromonas gingivalis
. The compiled
P. gingivalis
transcriptome profiles were based on total RNA samples isolated from three different laboratory culturing conditions, and the strand-specific transcription profiles generated covered the entire genome, including both protein coding and noncoding regions. The transcription profiles revealed various operon structures, 5′- and 3′-end untranslated regions (UTRs), differential expression patterns, and many novel, not-yet-annotated transcripts within intergenic and antisense regions. Further transcriptome analysis identified the majority of the genes as being expressed within operons and most 5′ and 3′ ends to be protruding UTRs, of which several 3′ UTRs were extended to overlap genes carried on the opposite/antisense strand. Extensive antisense RNAs were detected opposite most insertion sequence (IS) elements. Pairwise comparative analyses were also performed among transcriptome profiles of the three culture conditions, and differentially expressed genes and metabolic pathways were identified. With the growing realization that noncoding RNAs play important biological functions, the discovery of novel RNAs and the comprehensive transcriptome profiles compiled in this study may provide a foundation to further understand the gene regulation and virulence mechanisms in
P. gingivalis
. The transcriptome profiles can be viewed at and downloaded from the Microbial Transcriptome Database website,
http://bioinformatics.forsyth.org/mtd
.
Airway management in unconscious non-trauma patients
Authors: Nielsen Klaus , Hansen Christian Muff , Rasmussen Lars Simon 
Published: October 2011

BackgroundTracheal intubation is recommended in unconscious trauma patients to protect the airway from pulmonary aspiration of gastric contents and also to ensure ventilation and oxygenation. Unconsciousness is often defined as a Glasgow Coma Scale (GCS) score below 9. In non-trauma patients, however, there are no such firm recommendations regarding airway management and the GCS score may be less useful. The aim of this study was to describe the authors' experience with airway management in unconscious non-trauma patients in the prehospital setting with a physician-manned Mobile Emergency Care Unit (MECU). The main focus of the study was on the need for subsequent tracheal intubation during hospitalisation after initial treatment.MethodsThe study was based on an analysis of data prospectively collected from the MECU database in Copenhagen, Denmark. All unconscious (GCS scores below 9) non-trauma patients registered in the database during 2006 were included. The ambulance patient charts and medical records were scrutinised to assess outcome and the need for tracheal intubation during the first 24 h after admittance into hospital.ResultsA total of 557 unconscious non-trauma patients were examined and 129 patients (23%) were tracheally intubated by the MECU physician before or during transport to the hospital. Intubation was done in most patients with cardiac arrest, severe stroke or respiratory failure. Of the remaining 428 patients, 364 (85%) regained consciousness before being transported to the hospital, whereas 64 patients remained unconscious during transport and 12 (19%) of these were intubated in the emergency department.ConclusionsThe majority of unconscious non-trauma patients were not intubated in the prehospital setting. Unconscious non-trauma patients may not all need tracheal intubation before being transferred to hospital.
Patient based computational fluid dynamic characterization of carotid bifurcation stenosis before and after endovascular revascularization
Authors: Schirmer Clemens M , Malek Adel M 
Published: October 2011

IntroductionHemodynamic forces play a critical role in determining the molecular phenotype of the endothelial cell and in influencing vascular remodeling. A lesion based computational fluid dynamic (CFD) modeling approach is presented to understand the complex spatial and temporal hemodynamic changes that prevail in carotid stenosis (CS) in patients with critical CS undergoing carotid artery stenting (CAS).MethodsHigh resolution three-dimensional rotational angiography volumetric datasets were acquired before and after treatment in eight patients, segmented and used to generate a high quality structured hexahedral computational mesh with boundary layer refinement. CFD analysis was carried out using a time dependent laminar flow model implementing non-Newtonian realistic blood viscosity for blood, and used to compute wall shear stress (WSS) and its gradient (WSSG).ResultsCAS restored fully or near laminar flow in all cases in our series. In addition, WSS was found to decrease in the stented region in all cases, reduced to near normal levels of 34±14 dyn/cm2with significant blunting of the extreme pretreatment WSSG to levels lower than 1000 dyn/cm3.ConclusionsIn this series of patients with symptomatic CS, CFD simulation enabled estimation of the hemodynamic effect of CAS, leading to reversal of abnormal flow patterns and wall shear forces around the arterial stenosis, with normalization of flow laminarity and wall shear spatiotempotal patterns known to be associated with adverse endothelial cell function.
Sensitisation to common allergens and respiratory symptoms in endotoxin exposed workers: a pooled analysis
Authors: Basinas Ioannis , Schlünssen Vivi , Heederik Dick , Sigsgaard Torben , Smit Lidwien A M , Samadi Sadegh , Omland Øyvind , Hjort Charlotte , Madsen Anne Mette , Skov Simon , Wouters Inge M 
Published: October 2011

ObjectiveTo test the hypotheses that current endotoxin exposure is inversely associated with allergic sensitisation and positively associated with non-allergic respiratory diseases in four occupationally exposed populations using a standardised analytical approach.MethodsData were pooled from four epidemiological studies including 3883 Dutch and Danish employees in veterinary medicine, agriculture and power plants using biofuel. Endotoxin exposure was estimated by quantitative job-exposure matrices specific for the study populations. Dose–response relationships between exposure, IgE-mediated sensitisation to common allergens and self-reported health symptoms were assessed using logistic regression and generalised additive modelling. Adjustments were made for study, age, sex, atopic predisposition, smoking habit and farm childhood. Heterogeneity was assessed by analysis stratified by study.ResultsCurrent endotoxin exposure was dose-dependently associated with a reduced prevalence of allergic sensitisation (ORs of 0.92, 0.81 and 0.66 for low mediate, high mediate and high exposure) and hay fever (ORs of 1.16, 0.81 and 0.58). Endotoxin exposure was a risk factor for organic dust toxic syndrome, and levels above 100 EU/m3significantly increased the risk of chronic bronchitis (p<0.0001). Stratification by farm childhood showed no effect modification except for allergic sensitisation. Only among workers without a farm childhood, endotoxin exposure was inversely associated with allergic sensitisation. Heterogeneity was primarily present for biofuel workers.ConclusionsOccupational endotoxin exposure has a protective effect on allergic sensitisation and hay fever but increases the risk for organic dust toxic syndrome and chronic bronchitis. Endotoxin's protective effects are most clearly observed among agricultural workers.
Cancer mortality among female and male workers occupationally exposed to inorganic lead in the printing industry
Authors: Ilychova Svetlana A , Zaridze David G 
Published: October 2011

ObjectiveEvaluation of the carcinogenicity of lead for humans has been based primarily on the results of studies on occupationally exposed men, although gender differences in lead metabolism have been reported. In addition, most of the previous studies have been limited by a failure to identify and control for co-exposures to other known occupational carcinogens. The present study follows an industrial cohort of workers, mostly women, with moderate lead exposure and no confounding by other occupational exposures.MethodsWorkers, employed at least 2 years between 1950 and 1978 in manual and mechanical (linotype) typesetting and type foundries in 27 printing plants in Moscow, were included in the cohort, which comprised 1423 men and 3102 women. The cohort was followed up during 1979–2003 and contributed 93 682 person-years of observation. Follow-up was 97.7% complete. Standardised mortality ratios (SMRs) and 95% CIs, based on mortality rates of the Moscow general population and adjusted for gender, age and calendar time, were calculated for the total cohort as well as subcohorts stratified by various exposure parameters.ResultsAmong women, mortality from all causes, circulatory diseases and all cancers combined was lower than that in the Moscow general population and was similar across work groups. Among men, there was excess overall mortality, mainly due to increased mortality from ischaemic heart disease. For both sexes, no significant excess risk for any cancer site was observed, although some dose–response patterns were found. In the overall cohort, mortality from cancers of the kidney and pancreas increased up to twofold in the highest tertile of cumulative lead exposure based on duration and a relative ranking of the three subcohorts (9 deaths; SMR=2.12, 95% CI 1.10 to 4.07) and (18 deaths; SMR=2.32, 95% CI 1.46 to 3.68), respectively. Similar mortality trends for these two cancers were found in analyses by gender.ConclusionsConsistencies by sex and exposure level make a strong case for a link between exposure to inorganic lead and cancers of the kidney and pancreas.
The effect of resident peer-to-peer education on compliance with urinary catheter placement indications in the emergency department
Authors: Dyc Nicholas G , Pena Margarita E , Shemes Stephen P , Rey Janice E , Szpunar Susan M , Fakih Mohamad G 
Published: October 2011

ABSTRACT

Objective
This study aims to evaluate the effect of resident peer-to-peer education on knowledge of appropriate urinary catheter (UC) placement in the emergency department (ED) and to determine if this translates into further reduction in UC utilisation.

Background
Instituting guidelines for appropriate UC placement reduces UC utilisation in the ED. No study has explored if resident education in a teaching hospital would further reduce UC utilisation.

Methods
An educational intervention implemented in February 2009 consisted of a lecture, distribution of pocket cards and a peer-administered weekly review of institutional UC guidelines. A 12-question multiple-choice test was given to residents prelecture and postlecture, and the 12-question test was repeated 3 months later. Retrospective chart review was performed to evaluate UC utilisation before, immediately after and 3 months after the educational intervention.

Results
30 residents completed all three tests. Significant differences were found between the mean test score pre-education and the mean test score immediately after education (9.43±1.17 vs 10.87±1.46, p&lt;0.001) and between the mean test score pre-education and the mean test score 3 months posteducation (9.43±1.17 vs 10.43±1.28, p&lt;0.001). There was no significant difference in UC utilisation or in the proportion of indicated UCs placed by residents within the three study periods.

Conclusions
Resident peer-to-peer education was associated with improvement of knowledge but did not result in decreased UC utilisation. A more active approach must be taken and other factors need to be further explored to reduce unnecessary placement of UC by residents in the ED.
Prevalence of and risk factors for syphilis in Brazilian armed forces conscripts: Table 1
Authors: Ribeiro Denis , Rezende Erika Fazito , Pinto Valdir Monteiro , Mendes Pereira Gerson Fernando , Miranda Angélica Espinosa 
Published: October 2011

ObjectiveThe aim of this study was to describe the prevalence of syphilis by geographical region and the frequency of behaviours and symptoms related to sexually transmitted diseases (STD).MethodsA cross-sectional study was performed with Brazilian conscripts in 2007. They answered a self-administered questionnaire on demographic issues, sexual practices, condom use and STD symptoms. They had a blood sample collected for a syphilis test.ResultsA total of 35 460 conscripts answered the questionnaire and 75.5% reported previous sexual intercourse. Overall syphilis prevalence was 0.53% (95% CI 0.45% to 0.61%). By geographical region: northern (0.85%), northeast (0.82%), midwest (0.49%), southeast (0.34%) and southern region (0.26%). The final logistic regression model showed an association among having had syphilis and being 17 years old (OR 1.3; 95% CI 1.05 to 1.73), having up to 8 years of schooling (OR 1.5; 95% CI 1.03 to 2.22), living in the northern/northeast region (OR 1.2; 95% CI 1.04 to 1.36), being men who have sex with men (OR 4.5; 95% CI 2.59 to 7.81), reporting a previous history of STD (OR 2.7; 95% CI 1.03 to 6.99) and genital ulcers (OR 2.6; 95% CI 1.59 to 4.26).ConclusionsAddressing young people at the time of military enlistment may be a good time to consider new strategies for accessing and counselling this population, thus allowing the implementation of a more appropriate healthcare policy.
The LMP7-K Allele of the Immunoproteasome Exhibits Reduced Transcript Stability and Predicts High Risk of Colon Cancer
Authors: Fellerhoff Barbara , Gu Songhai , Laumbacher Barbara , Nerlich Andreas G. , Weiss Elisabeth H. , Glas Jürgen , Kopp Reinhard , Johnson Judith P. , Wank Rudolf 
Published: October 2011

Abstract
Destruction of cancer cells by cytotoxic T lymphocytes depends on immunogenic tumor peptides generated by proteasomes and presented by human leukocyte antigen (HLA) molecules. Functional differences arising from alleles of immunoproteasome subunits have not been recognized so far. We analyzed the genetic polymorphism of the immunoproteasome subunits LMP2 and LMP7 and of the transporters associated with antigen processing (TAP1 and TAP2) in two independently collected panels of colorectal carcinoma patients (N1 = 112, N2 = 62; controls, N = 165). High risk of colon cancer was associated with the LMP7-K/Q genotype (OR = 8.10, P = 1.10 × 10−11) and low risk with the LMP7-Q/Q genotype (OR = 0.10, P = 5.97 × 10−13). The basis for these distinct associations of LMP7 genotypes was functionally assessed by IFN-γ stimulation of colon carcinoma cell lines (N = 10), followed by analyses of mRNA expression of HLA class I, TAP1, TAP2, and LMP7, with real-time PCR. Whereas induction of HLA-B, TAP1, and TAP2 was comparable in all cell lines, transcript amounts of LMP7-Q increased 10-fold, but of LMP7-K only 3.8-fold. This correlated with a reduced transcript stability of LMP7-K (t½ ≈ 7 minutes) compared with LMP7-Q (t½ ≈ 33 minutes). In addition, LMP7-Q/Q colon carcinoma cells increased (the peptide based) HLA class I surface expression significantly after IFN-γ stimulation, whereas LMP7-Q/K and LMP7-K/K carcinoma cells showed minimal (&lt;20%) changes. These results suggest that the presence of LMP7-K can reduce the formation of immunoproteasomes and thus peptide processing, followed by reduced peptide–HLA presentation, a crucial factor in the immune response against cancer. Cancer Res; 71(23); 7145–54. ©2011 AACR.
Thrombospondin-1 Triggers Cell Migration and Development of Advanced Prostate Tumors
Authors: Firlej Virginie , Mathieu Jacques R.R. , Gilbert Cristèle , Lemonnier Loïc , Nakhlé Jessica , Gallou-Kabani Catherine , Guarmit Basma , Morin Aurélie , Prevarskaya Natalia , Delongchamps Nicolas Barry , Cabon Florence 
Published: October 2011

Abstract
The antitumor effects of pharmacologic inhibitors of angiogenesis are hampered in patients by the rapid development of tumor resistance, notably through increased invasiveness and accelerated metastasis. Here, we reevaluated the role of the endogenous antiangiogenic thrombospondin 1 (TSP1) in prostate carcinomas in which angiogenesis is an active process. In xenografted tumors, we observed that TSP1 altogether inhibited angiogenesis and fostered tumor development. Our results show that TSP1 is a potent stimulator of prostate tumor cell migration. This effect required CD36, which also mediates TSP1 antiangiogenic activity, and was mimicked by an antiangiogenic TSP1-derived peptide. As suspected for pharmacologic inhibitors of angiogenesis, the TSP1 capacities to increase hypoxia and to trigger cell migration are thus inherently linked. Importantly, although antiangiogenic TSP1 increases hypoxia in vivo, our data show that, in turn, hypoxia induced TSP1, thus generating a vicious circle in prostate tumors. In radical prostatectomy specimens, we found TSP1 expression significantly associated with invasive tumors and with tumors which eventually recurred. TSP1 may thus help select patients at risk of prostate-specific antigen relapse. Together, the data suggest that intratumor disruption of the hypoxic cycle through TSP1 silencing will limit tumor invasion. Cancer Res; 71(24); 7649–58. ©2011 AACR.
Plasminogen Receptor S100A10 Is Essential for the Migration of Tumor-Promoting Macrophages into Tumor Sites
Authors: Phipps Kyle D. , Surette Alexi P. , O'Connell Paul A. , Waisman David M. 
Published: October 2011

Abstract
Macrophages are critical drivers of tumor growth, invasion, and metastasis. Movement of macrophages into tumors requires the activity of cell surface proteases such as plasmin. In this study, we offer genetic evidence that plasminogen receptor S100A10 is essential for recruitment of macrophages to the tumor site. Growth of murine Lewis lung carcinomas or T241 fibrosarcomas was dramatically reduced in S100A10-deficient mice compared with wild-type mice. The tumor growth deficit corresponded with a decrease in macrophage density that could be rescued by intraperitoneal injection of wild-type but not S100A10-deficient macrophages. Notably, macrophages of either genotype could rescue tumor growth if they were injected into the tumor itself, establishing that S100A10 was required specifically for the migratory capability needed for tumor homing. Conversely, selective depletion of macrophages from wild-type mice phenocopied the tumor growth deficit seen in S100A10-deficient mice. Together, our findings show that S100A10 is essential and sufficient for macrophage migration to tumor sites, and they define a novel rate-limiting step in tumor progression. Cancer Res; 71(21); 6676–83. ©2011 AACR.
Cyclin D3 Compensates for the Loss of Cyclin D1 during ErbB2-Induced Mammary Tumor Initiation and Progression
Authors: Zhang Qian , Sakamoto Kazuhito , Liu Chengbao , Triplett Aleata A. , Lin Wan-chi , Rui Hallgeir , Wagner Kay-Uwe 
Published: October 2011

Abstract
Cyclin D1 regulates cell proliferation and is a candidate molecular target for breast cancer therapy. This study addresses whether Cyclin D1 is indispensable for ErbB2-associated mammary tumor initiation and progression using a breast cancer model in which this cell-cycle regulator can be genetically ablated prior to or after neoplastic transformation. Deficiency in Cyclin D1 delayed tumor onset but did not prevent the occurrence of mammary cancer in mice overexpressing wild-type ErbB2. The lack of Cyclin D1 was associated with a compensatory upregulation of Cyclin D3, which explains why the targeted downregulation of Cyclin D1 in established mammary tumors had no effect on cancer cell proliferation. Cyclin D1 and D3 are overexpressed in human breast cancer cell lines and primary invasive breast cancers, and Cyclin D3 frequently exceeded the expression of Cyclin D1 in ErbB2-positive cases. The simultaneous inhibition of both cyclins in mammary tumor cells reduced cancer cell proliferation in vitro and decreased the tumor burden in vivo. Collectively, the results of this study suggest that only the combined inhibition of Cyclin D1 and D3 might be a suitable strategy for breast cancer prevention and therapy. Cancer Res; 71(24); 7513–24. ©2011 AACR.