bluuebunny/crossref_metadata_2025_split huggingface dataset:
Involvement of Fe Uptake Systems and AmpC β-Lactamase in Susceptibility to the Siderophore Monosulfactam BAL30072 in Pseudomonas aeruginosa
Authors: van Delden Christian , Page Malcolm G. P. , Köhler Thilo 
Published: February 2013

ABSTRACT

BAL30072 is a monosulfactam conjugated with an iron-chelating dihydroxypyridone moiety. It is active against Gram-negative bacteria, including multidrug-resistant
Pseudomonas aeruginosa
. We selected mutants with decreased susceptibilities to BAL30072 in
P. aeruginosa
PAO1 under a variety of conditions. Under iron-deficient conditions, mutants with overexpression of AmpC β-lactamase predominated. These mutants were cross-resistant to aztreonam and ceftazidime. Similar mutants were obtained after selection at >16× the MIC in iron-sufficient conditions. At 4× to 8× the MIC, mutants with elevated MIC for BAL30072 but unchanged MICs for aztreonam or ciprofloxacin were selected. The expression of
ampC
and the major efflux pump genes were also unchanged. These BAL30072-specific mutants were characterized by transcriptome analysis, which revealed upregulation of the Fe-dicitrate operon, FecIRA. Whole-genome sequencing showed that this resulted from a single nucleotide change in the Fur-box of the
fecI
promoter. Overexpression of either the FecI ECF sigma factor or the FecA receptor increased BAL30072 MICs 8- to 16-fold. A
fecI
mutant and a
fecA
mutant of PAO1 were hypersusceptible to BAL30072 (MICs < 0.06 μg/ml). The most downregulated gene belonged to the pyochelin synthesis operon, although mutants in pyochelin receptor or synthesis genes had unchanged MICs. The
piuC
gene, coding for a Fe(II)-dependent dioxygenase located next to the
piuA
iron receptor gene, was also downregulated. The MICs of BAL30072 for
piuC
and
piuA
transposon mutants were increased 8- and 16-fold, respectively. We conclude that the upregulation of the Fe-dicitrate system impacts the expression of other TonB-dependent iron transporters and that PiuA and PiuC contribute to the susceptibility of
P. aeruginosa
PAO1 to BAL30072.
Trichomonas vaginalis Contact-Dependent Cytolysis of Epithelial Cells
Authors: Lustig Gila , Ryan Christopher M. , Secor W. Evan , Johnson Patricia J. 
Published: February 2013

ABSTRACT

Trichomonas vaginalis
is an extracellular protozoan parasite that binds to the epithelium of the human urogenital tract during infection. In this study, we examined the propensities of 26
T. vaginalis
strains to bind to and lyse prostate (BPH-1) and ectocervical (Ect1) epithelium and to lyse red blood cells (RBCs). We found that only three of the strains had a statistically significant preference for either BPH-1 (MSA1103) or Ect1 (LA1 and MSA1123). Overall, we observed that levels of adherence are highly variable among strains, with a 12-fold range of adherence on Ect1 cells and a 45-fold range on BPH-1 cells. Cytolysis levels displayed even greater variability, from no detectable cytolysis to 80% or 90% cytolysis of Ect1 and BPH-1, respectively. Levels of adherence and cytolysis correlate for weakly adherent/cytolytic strains, and a threshold of attachment was found to be necessary to trigger cytolysis; however, this threshold can be reached without inducing cytolysis. Furthermore, cytolysis was completely blocked when we prevented attachment of the parasites to host cells while allowing soluble factors complete access. We demonstrate that hemolysis was a rare trait, with only 4 of the 26 strains capable of lysing >20% RBCs with a 1:30 parasite/RBC ratio. Hemolysis also did not correlate with adherence to or cytolysis of either male (BPH-1)- or female (Ect1)-derived epithelial cell lines. Our results reveal that despite a broad range of pathogenic properties among different
T. vaginalis
strains, all strains show strict contact-dependent cytolysis.
Effect of the Leptin Receptor Q223R Polymorphism on the Host Transcriptome following Infection with Entamoeba histolytica
Authors: Mackey-Lawrence Nicole M. , Guo Xiaoti , Sturdevant Daniel E. , Virtaneva Kimmo , Hernandez Matthew M. , Houpt Eric , Sher Alan , Porcella Stephen F. , Petri William A. 
Published: February 2013

ABSTRACT

Resistance to amebiasis is associated with a polymorphism in the leptin receptor. Previous studies demonstrated that humans with the ancestral Q223 leptin receptor allele were nearly four times less likely to be infected with
Entamoeba histolytica
than those carrying the mutant R223 allele. We hypothesized that the Q223 allele protected against
E. histolytica
via STAT3-mediated transcription of genes required for mucosal immunity. To test this, mice containing the humanized
LEPR
Q or R allele at codon 223 were intracecally infected with
E. histolytica
. Susceptibility to amebiasis was assessed, and cecal tissues were analyzed for changes in gene expression. By 72 h postchallenge, all Q223 mice had cleared
E. histolytica
, whereas 39% of 223R mice were infected. Thirty-seven genes were differentially expressed in response to infection at 72 h, including proinflammatory genes (
CXCL2
,
S100A8/9
,
PLA2G7
,
ITBG2
, and
MMP9
) and functions pertaining to the movement and activity of immune cells. A comparison at 12 h postchallenge of infected Q223 versus R223 mice identified a subset of differentially expressed genes, many of which were closely linked to leptin signaling. Further analyses indicated that the Q223 gene expression pattern was consistent with a suppressed apoptotic response to infection, while 223R showed increased cellular proliferation and recruitment. These studies are the first to illuminate the downstream effects of leptin receptor polymorphisms on intestinal infection by
E. histolytica
. As such, they are important for the insight that they provide into this previously uncharacterized mechanism of mucosal immunity.
A Quorum-Sensing-Induced Bacteriophage Defense Mechanism
Authors: Høyland-Kroghsbo Nina Molin , Mærkedahl Rasmus Baadsgaard , Svenningsen Sine Lo 
Published: February 2013

ABSTRACT

One of the key determinants of the size, composition, structure, and development of a microbial community is the predation pressure by bacteriophages. Accordingly, bacteria have evolved a battery of antiphage defense strategies. Since maintaining constantly elevated defenses is costly, we hypothesize that some bacteria have additionally evolved the abilities to estimate the risk of phage infection and to adjust their strategies accordingly. One risk parameter is the density of the bacterial population. Hence, quorum sensing, i.e., the ability to regulate gene expression according to population density, may be an important determinant of phage-host interactions. This hypothesis was investigated in the model system of
Escherichia coli
and phage λ. We found that, indeed, quorum sensing constitutes a significant, but so far overlooked, determinant of host susceptibility to phage attack. Specifically,
E. coli
reduces the numbers of λ receptors on the cell surface in response to
N
-acyl-
l
-homoserine lactone (AHL) quorum-sensing signals, causing a 2-fold reduction in the phage adsorption rate. The modest reduction in phage adsorption rate leads to a dramatic increase in the frequency of uninfected survivor cells after a potent attack by virulent phages. Notably, this mechanism may apply to a broader range of phages, as AHLs also reduce the risk of χ phage infection through a different receptor.

IMPORTANCE
To enable the successful manipulation of bacterial populations, a comprehensive understanding of the factors that naturally shape microbial communities is required. One of the key factors in this context is the interactions between bacteria and the most abundant biological entities on Earth, namely, the bacteriophages that prey on bacteria. This proof-of-principle study shows that quorum sensing plays an important role in determining the susceptibility of
E. coli
to infection by bacteriophages λ and χ. On the basis of our findings in the classical
Escherichia coli
-λ model system, we suggest that quorum sensing may serve as a general strategy to protect bacteria specifically under conditions of high risk of infection.
SILK flow diverter for treatment of intracranial aneurysms: initial experience and cost analysis
Authors: Shankar Jai Jai Shiva , Vandorpe Robert , Pickett Gwynedd , Maloney William 
Published: February 2013

BackgroundThe flow diverting stent is a new and expansive tool in the endovascular therapy of complex intracranial aneurysms. We present our experience using SILK flow diverter (SFD) in patients with complex intracranial aneurysms, and a cost analysis.MethodsBetween September 2010 and May 2012, 19 consecutive patients with 29 complex intracranial aneurysms were treated with SFD without the adjunctive use of coils. We retrospectively evaluated the technical aspects, thromboembolic events, adjunctive therapies, and short term results in patients with complex intracranial aneurysms treated with SFD. A cost analysis of patients who were treated with SFD was performed and compared with similar sized aneurysms coiled with stent assisted coiling.ResultsThe primary technical success rate was 100%. An adjunctive device was required in two of our patients. The technique related complication rate and the 30 day mortality and morbidity rates were 5% (1/20) and 10% (2/20), respectively. We had a total of 263 patient months of clinical and 166 patient months of imaging follow-up. Follow-up imaging revealed two asymptomatic occlusions of the parent artery. Complete occlusion of the aneurysm with fully patent parent artery was observed in 59% of patients where follow-up images were available. The cost analysis showed that the mean cost of treatment with SFD was significantly cheaper compared with the presumed cost of stent assisted coiling (p<0.001).ConclusionsThe SFD provides a very feasible, efficient, relatively safe, and cost effective method to treat complex intracranial aneurysms without the use of adjunct coiling.
Cenozoic pure-shear collapse of the southern Menderes Massif, Turkey
Authors: Iredale Lindsay J. , Teyssier Christian , Whitney Donna L. 
Published: February 2013

Abstract

A transition from construction to collapse of the Alpine orogen in Middle to Late Eocene time is recorded in the structural fabrics of gneissic rocks in the southern Menderes Massif, western Turkey. Augen gneiss in the southern Menderes Massif indicates a spatial switch of shear sense along a north–south section through the complex (top-to-north shear in the north and top-to-south in the south). This ‘kinematic hinge’ corresponds to a broad zone of dominant pure shear where crust underwent vertical thinning and approximate north–south extension. During this extension, foliation became corrugated with fold axes parallel to lineation, indicating inflow from neighbouring crust to the east and the west. Published geochronologic work suggests a Middle to Late Eocene age for this dominant fabric. Thermal weakening of felsic Menderes crust beneath Alpine nappes may have triggered this orogenic collapse. Deformation fabrics developed at temperatures of
c.
550 °C, and progressive cooling during collapse generated strain localization within a kilometre-thick shear zone at the southern margin of the Menderes Massif. In the southern Menderes, the corrugation of foliation indicates that Middle to Late Eocene flow was constricted into an orogen-perpendicular direction. This behaviour is similar to the collapse and orogen-parallel extension of the European Alps (Lepontine dome, Tauern Window).
Late Palaeozoic–Cenozoic tectonic development of carbonate platform, margin and oceanic units in the Eastern Taurides, Turkey
Authors: Robertson A. H. F. , Parlak O. , Metİn Y. , Vergİlİ Ö. , Tasli K. , İnan N. , Soycan H. 
Published: February 2013

Abstract
Continental margin-type, ophiolitic and mélange units are exposed throughout central eastern Turkey (e.g. Gürün, Hekimhan and Pınarbaşı areas). These restore as a north-verging Triassic-rifted continental margin that underwent Jurassic–Early Cretaceous passive margin subsidence. Chemically ‘enriched’ basaltic lavas of seamount type are interbedded with and overlain by Middle Jurassic–Early Cretaceous ribbon cherts. Ophiolitic rocks (e.g. Pınarbaşı, Dağlıca, Kuluncak, Hekimhan, Divriği) formed by spreading above a Late Cretaceous northwards-dipping intra-oceanic subduction zone. Emplacement of continental margin units, mélanges and ophiolites onto the East Tauride platform was driven by trench-margin collision during latest Cretaceous. The northern part of the East Tauride neritic carbonate platform detached and overthrust the continent to the south (Malatya Metamorphics) which was deeply underthrust, metamorphosed at least to greenschist facies and exhumed by latest Cretaceous. Collision-related Mid-Eocene southwards thrusting strongly affected the western part of the region (e.g. Pınarbaşı), whereas areas further east (e.g. Darende, Hekimhan, Divriği, Sivas) mainly experienced folding. Taking account of the regional tectonic setting, we infer that the Gürün platform, with its distinctive unbroken up to Lutetian-aged succession, represents a small exotic terrane that was translated from a relatively southerly (‘internal’) part of the Tauride platform (Geyik Dağ), related to strike-slip displacement (syn/post-Eocene to pre-Pliocene).

Supplementary material:

Two supplementary tables giving the GPS coordinates of the samples of basic intrusive and extrusive igneous rocks that were analyzed during this work are available at
www.geolsoc.org.uk/SUP18569
Plio-Quaternary stress regime in Eşen Çay Basin, SW Turkey
Authors: Över Semir , Özden Süha , Yilmaz Hüseyin , Pinar Ali , Ünlügenç Ulvi Can , Kamaci Zuheyr 
Published: February 2013

Abstract

The Plio-Quaternary Eşen Çay Basin is situated at the junction of Hellenic and Cyprus arcs in southwestern Turkey. The basin is important for understanding the tectonic evolution of the region in relation to the Hellenic and Cyprus arcs. Fault data from unconsolidated Pliocene and Quaternary deposits, as well as from pre-Pliocene lithologies, are analysed in order to reconstruct the evolution of the stress field evolution from Pliocene onwards. Inversion of measured fault slip vector data identifies two main stress states: extensional and strike-slip. Both states are characterized by a NE–SW-trending minimum horizontal stress axis (σ
Hmin
=σ
3
). The mean
R
value is 0.67, indicating a triaxial state of stress. The inversion also indicates the existence of extensional and strike-slip faulting characterized by a NW–SE-trending σ
3
axis. This indicates a change in the direction of the minimum horizontal stress axis (σ
3
) from a NW–SE-trending σ
3
that dominated prior to Quaternary to a NE–SW-trending σ
3
that dominated during Quaternary up to actual time.
New Strategies in Diagnosing Cancer in Thyroid Nodules: Impact of Molecular Markers
Authors: Nikiforov Yuri E. , Yip Linwah , Nikiforova Marina N. 
Published: February 2013

Abstract
Thyroid cancer is the most common type of endocrine malignancy, with approximately 55,000 new cases diagnosed in the United States in 2012. However, thyroid nodules are much more prevalent, particularly with increased age, and only a small fraction of those are malignant. Therefore, the major clinical challenge is to reliably differentiate those nodules that are malignant and need to be treated surgically from the majority of nodules that are benign and do not require surgery. The traditional diagnostic approach to this clinical situation is ultrasound-guided fine-needle aspiration (FNA) of the thyroid nodule followed by cytologic examination, which together reliably establish the diagnosis in 70% to 80% of cases. However, in the rest of nodules the presence of cancer cannot be ruled out by FNA cytology, hampering appropriate surgical management and frequently resulting in unnecessary surgical interventions. New approaches to diagnosis of cancer in thyroid nodules are based on mutational and other molecular markers, which can be reliably detected in cells aspirated during the FNA procedure. These markers offer significant improvement in the diagnostic accuracy of FNA cytology and are poised to make a profound effect on the management of patients with thyroid nodules. In addition to the molecular markers that have recently become available for clinical use, rapid development of new sequencing techniques is expected to further improve the accuracy of cancer diagnosis in thyroid nodules and allow for a fully individualized approach to the management of patients with thyroid nodules. Clin Cancer Res; 19(9); 2283–8. ©2013 AACR.
Promoter CpG Island Hypermethylation of the DNA Repair Enzyme MGMT Predicts Clinical Response to Dacarbazine in a Phase II Study for Metastatic Colorectal Cancer
Authors: Amatu Alessio , Sartore-Bianchi Andrea , Moutinho Catia , Belotti Alessandro , Bencardino Katia , Chirico Giuseppe , Cassingena Andrea , Rusconi Francesca , Esposito Anna , Nichelatti Michele , Esteller Manel , Siena Salvatore 
Published: February 2013

Abstract
Purpose: O6-methylguanine-DNA-methyltransferase (MGMT) is a DNA repair protein removing mutagenic and cytotoxic adducts from O6-guanine in DNA. Approximately 40% of colorectal cancers (CRC) display MGMT deficiency due to the promoter hypermethylation leading to silencing of the gene. Alkylating agents, such as dacarbazine, exert their antitumor activity by DNA methylation at the O6-guanine site, inducing base pair mismatch; therefore, activity of dacarbazine could be enhanced in CRCs lacking MGMT. We conducted a phase II study with dacarbazine in CRCs who had failed standard therapies (oxaliplatin, irinotecan, fluoropyrimidines, and cetuximab or panitumumab if KRAS wild-type).
Experimental Design: All patients had tumor tissue assessed for MGMT as promoter hypermethylation in double-blind for treatment outcome. Patients received dacarbazine 250 mg/m2 intravenously every day for four consecutive days, every 21 days, until progressive disease or intolerable toxicity. We used a Simon two-stage design to determine whether the overall response rate would be 10% or more. Secondary endpoints included association of response, progression-free survival, and disease control rate with MGMT status.
Results: Sixty-eight patients were enrolled from May 2011 to March 2012. Patients received a median of three cycles of dacarbazine (range 1–12). Grades 3 and 4 toxicities included: fatigue (41%), nausea/vomiting (29%), constipation (25%), platelet count decrease (19%), and anemia (18%). Overall, two patients (3%) achieved partial response and eight patients (12%) had stable disease. Disease control rate (partial response + stable disease) was significantly associated with MGMT promoter hypermethylation in the corresponding tumors.
Conclusion: Objective clinical responses to dacarbazine in patients with metastatic CRC are confined to those tumors harboring epigenetic inactivation of the DNA repair enzyme MGMT. Clin Cancer Res; 19(8); 2265–72. ©2013 AACR.
Combined Serum CA19-9 and miR-27a-3p in Peripheral Blood Mononuclear Cells to Diagnose Pancreatic Cancer
Authors: Wang Wan-Sheng , Liu Ling-Xiao , Li Guo-Ping , Chen Yi , Li Chang-Yu , Jin Da-Yong , Wang Xiao-Lin 
Published: February 2013

Abstract
MicroRNAs are potentially very useful biomarkers in the diagnosis of cancer. We sought to identify specific microRNAs in peripheral blood mononuclear cells (PBMCs) whose levels might facilitate diagnosis of pancreatic cancer. We investigated PBMC microRNA expression in three independent cohorts [healthy, benign pancreatic/peripancreatic diseases (BPD), and pancreatic cancer], comprising a total of 352 participants. First, we used sequencing technology to identify differentially expressed microRNAs in PBMC of pancreatic cancer, BPD, and healthy controls (n = 20 in each group). Then the selected microRNAs were analyzed using the quantitative reverse transcriptase PCR assays in the remaining 292 samples. The predictive value of the microRNAs was evaluated by logistic regression models and the receiver operating characteristic curve (AUC). We found that miR-27a-3p level in PBMCs could discriminate pancreatic cancer from BPD with a sensitivity of 82.2% and specificity of 76.7% (AUC = 0.840; 95% CI, 0.787–0.885%). Combination of PBMC miR-27a-3p and serum CA19-9 levels provided a higher diagnostic accuracy with a sensitivity of 85.3% and specificity of 81.6% (AUC = 0.886; 95% CI, 0.837–0.923%). The satisfactory diagnostic performance of the panel persisted regardless of disease status (AUCs for tumor-node-metastasis stages I–III were 0.881, 0.884, and 0.893, respectively). PBMC miR-27a-3p level represents a potential marker for pancreatic cancer screening. A panel combining serum CA19-9 and PBMC miR-27a-3p level could have considerable clinical value in diagnosing pancreatic cancer. Cancer Prev Res; 6(4); 331–8. ©2013 AACR.
Fifteen-Year Trends in Awareness of Heart Disease in Women
Authors: Mosca Lori , Hammond Gmerice , Mochari-Greenberger Heidi , Towfighi Amytis , Albert Michelle A. 
Published: February 2013

Background—
The purpose of this study was to evaluate trends in awareness of cardiovascular disease (CVD) risk among women between 1997 and 2012 by racial/ethnic and age groups, as well as knowledge of CVD symptoms and preventive behaviors/barriers.

Methods and Results—

A study of awareness of CVD was conducted by the American Heart Association in 2012 among US women >25 years of age identified through random-digit dialing (n=1205) and Harris Poll Online (n=1227), similar to prior American Heart Association national surveys. Standardized questions on awareness were given to all women; additional questions about preventive behaviors/barriers were given online. Data were weighted, and results were compared with triennial surveys since 1997. Between 1997 and 2012, the rate of awareness of CVD as the leading cause of death nearly doubled (56% versus 30%;
P
<0.001). The rate of awareness among black and Hispanic women in 2012 (36% and 34%, respectively) was similar to that of white women in 1997 (33%). In 1997, women were more likely to cite cancer than CVD as the leading killer (35% versus 30%), but in 2012, the trend reversed (24% versus 56%). Awareness of atypical symptoms of CVD has improved since 1997 but remains low. The most common reasons why women took preventive action were to improve health and to feel better, not to live longer.

Conclusions—
Awareness of CVD among women has improved in the past 15 years, but a significant racial/ethnic minority gap persists. Continued effort is needed to reach at-risk populations. These data should inform public health campaigns to focus on evidenced-based strategies to prevent CVD and to help target messages that resonate and motivate women to take action.