bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Accessory Genome of
Pseudomonas aeruginosa
Authors: Kung Vanderlene L. , Ozer Egon A. , Hauser Alan R. 
Published: November 2010

SUMMARY

Pseudomonas aeruginosa
strains exhibit significant variability in pathogenicity and ecological flexibility. Such interstrain differences reflect the dynamic nature of the
P. aeruginosa
genome, which is composed of a relatively invariable “core genome” and a highly variable “accessory genome.” Here we review the major classes of genetic elements comprising the
P. aeruginosa
accessory genome and highlight emerging themes in the acquisition and functional importance of these elements. Although the precise phenotypes endowed by the majority of the
P. aeruginosa
accessory genome have yet to be determined, rapid progress is being made, and a clearer understanding of the role of the
P. aeruginosa
accessory genome in ecology and infection is emerging.
Ductile duplexes as potential natural gas plays: an example from the Appalachian thrust belt in Georgia, USA
Authors: Cook Brian S. , Thomas William A. 
Published: November 2010

Abstract

In a well-defined small-scale recess in the Appalachian thrust belt in northwestern Georgia (USA), two distinct regional strike directions intersect at
c.
50°. Fault intersections and interference folds enable tracing of both structural strikes. Around the recess, tectonically thickened weak stratigraphic layers – shales of the Cambrian Conasauga Formation – accommodated ductile deformation associated with the folding and faulting of the overlying Cambrian–Ordovician regional competent layer. The structures in the competent layer are analogous to those over ductile duplexes documented along strike to the SW in Alabama, where gas production has been established from the deformed shale. The analogy with structures in Alabama suggests a ductile duplex and natural gas potential within the recess in Georgia.

The tectonic thickening of the weak-layer shales is evident in palinspastically restored cross sections, which demonstrate a nearly 100% increase in volume over the restored state cross sections. The dominant cause of the surplus shale volume is likely pre-thrusting deposition of thick shale in a basement graben that was later inverted. The volume balance of the ductile duplex is critical for palinspastic reconstruction of the recess, and for the kinematic history and mechanics of the ductile duplex.
Controls on lateral structural variability along the Keping Shan Thrust Belt, SW Tien Shan Foreland, China
Authors: Turner Sebastian A. , Cosgrove John W. , Liu Jian G. 
Published: November 2010

Abstract
Lateral structural variability and partitioning of fold–thrust belts often reflects lateral variations in the stratigraphy of the deforming foreland and interaction with inherited structures. The Keping Shan Thrust Belt, NW China, was initiated during the late Cenozoic and is a spectacular example of contractional deformation in a foreland setting. The belt is characterized by a series of imbricate thrusts which form a broadly arcuate salient and deform the thick (3–6 km) Phanerozoic sedimentary succession of the NW Tarim Basin (SW Tien Shan foreland). Abrupt lateral changes in the thickness of the sedimentary succession are associated with a series of major pre-existing basement faults which cross-cut the belt and which were probably initiated during early Permian times. These lateral variations in the basin template have impacted strongly on the structural architecture of the superimposed thrust belt. Variations in the thickness of the sediment pile affect the spatial distribution of thrusts, which increase in abundance where the sediment is thinnest. The inherited cross-cutting basement faults and the associated abrupt changes in sediment thickness combine to generate partitioning of the thrust belt.
Thrust belt architecture of the central and southern Western Foothills of Taiwan
Authors: Rodriguez-Roa Fernando A. , Wiltschko David V. 
Published: November 2010

Abstract

An internally consistent 3D structural model for the central and southern Western Foothills Fold and Thrust Belt (WFFTB) was constructed from serial balanced cross sections. The level of exposure, thrust sheet thickness and degree of internal complexity observed within the WFFTB are influenced by the presence of pre-existing normal faults. Most of the faults of the Western Foothills started their activity before the deposition of the Cholan Formation (
c
. 3.5 Ma). Out-of-sequence faulting is common and may be due to localized erosion and fault inversion. Basement appears to be more significantly involved towards the south where a new structure, the sub-Yuching uplift, has been identified. The estimated aggregate displacement on WFFTB thrusts is uniformly about 40 km on the central segment cross sections, even in the region of greatest basement involvement. Total thrust displacement starts to decrease on the southernmost cross sections, which may be coincident with the transition from collision in the north to accretion. The restored position of the pre-existing normal faults places them as far east as the present-day Coastal Range. The WFFTB rocks must have been stripped off the Eurasian margin before significant burial could take place.
Demethylation of RB Regulator MYPT1 by Histone Demethylase LSD1 Promotes Cell Cycle Progression in Cancer Cells
Authors: Cho Hyun-Soo , Suzuki Takehiro , Dohmae Naoshi , Hayami Shinya , Unoki Motoko , Yoshimatsu Masanori , Toyokawa Gouji , Takawa Masashi , Chen Taiping , Kurash Julia K. , Field Helen I. , Ponder Bruce A.J. , Nakamura Yusuke , Hamamoto Ryuji 
Published: November 2010

Abstract
Histone demethylase LSD1 (also known as KDM1 and AOF2) is active in various cancer cells, but its biological significance in human carcinogenesis is unexplored. In this study, we explored hypothesized interactions between LSD1 and MYPT1, a known regulator of RB1 phosphorylation. We found that MYPT1 was methylated in vitro and in vivo by histone lysine methyltransferase SETD7 and demethylated by LSD1, identifying Lys 442 of MYPT1 as a target for methylation/demethylation by these enzymes. LSD1 silencing increased MYPT1 protein levels, decreasing the steady state level of phosphorylated RB1 (Ser 807/811) and reducing E2F activity. MYPT1 methylation status influenced the affinity of MYPT1 for the ubiquitin-proteasome pathway of protein turnover. MYPT1 was unstable in murine cells deficient in SETD7, supporting the concept that MYPT1 protein stability is physiologically regulated by methylation status. LSD1 overexpression could activate RB1 phosphorylation by inducing a destabilization of MYPT1 protein. Taken together, our results comprise a novel cell cycle regulatory mechanism mediated by methylation/demethylation dynamics, and they reveal the significance of LSD1 overexpression in human carcinogenesis. Cancer Res; 71(3); 655–60. ©2010 AACR.
Conditionally Replicating Adenovirus Expressing TIMP2 for Ovarian Cancer Therapy
Authors: Yang Sherry W. , Cody James J. , Rivera Angel A. , Waehler Reinhard , Wang Minghui , Kimball Kristopher J. , Alvarez Ronald A. , Siegal Gene P. , Douglas Joanne T. , Ponnazhagan Selvarangan 
Published: November 2010

Abstract
Purpose: Current treatments for ovarian cancer have limited therapeutic outcomes due to advanced stage of the disease at diagnosis. Among new therapies, conditionally replicating adenoviruses (CRAds), designed to selectively lyse cancer cells, hold promise. In clinical trials, CRAds exhibited limited efficacy thus far. Second-generation CRAds are being developed to express a therapeutic protein to enhance antitumor efficacy. One attractive target in the tumor microenvironment is the matrix metalloproteinases (MMPs) that degrade the extracellular matrix, and are upregulated in ovarian cancer. Tissue inhibitor of metalloproteinase 2 (TIMP2) is an endogenous inhibitor of MMPs. The present study developed and evaluated a novel CRAd (Ad5/3-CXCR4-TIMP2) for ovarian cancer therapy.
Experimental Design: A targeted CRAd, Ad5/3-CXCR4-TIMP2 was developed using the CXCR4 promoter for enhanced replication, and expressing the TIMP2 transgene. The efficacy of this armed CRAd was determined in both established human ovarian cancer cell lines and in primary ovarian tumor samples.
Results: Ad5/3-CXCR4-TIMP2 mediated expression of functional TIMP2, as demonstrated by the inhibition of MMP activity. In addition, arming with TIMP2 did not inhibit viral replication or oncolytic potency, as the TIMP2-armed viruses showed enhanced killing of cancer cells when compared to the unarmed viruses. We also examined viral replication in primary ovarian cancer tissues obtained from patients with stage III and IV ovarian cancer. In four of the five tumor samples, Ad5/3-CXCR4-TIMP2 revealed a 21- to 89-fold increase in replication when compared to the Ad5/3 virus.
Conclusion: Results support the translational potential of Ad5/3-CXCR4-TIMP2 for treatment of patients with advanced ovarian cancer. Clin Cancer Res; 17(3); 538–49. ©2010 AACR.
Enhancer of Zeste Homolog 2 Promotes the Proliferation and Invasion of Epithelial Ovarian Cancer Cells
Authors: Li Hua , Cai Qi , Godwin Andrew K. , Zhang Rugang 
Published: November 2010

Abstract
Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of the polycomb repressive complex 2 (PRC2) that includes noncatalytic subunits suppressor of zeste 12 (SUZ12) and embryonic ectoderm development (EED). When present in PRC2, EZH2 catalyzes trimethylation on lysine 27 residue of histone H3 (H3K27Me3), resulting in epigenetic silencing of gene expression. Here, we investigated the expression and function of EZH2 in epithelial ovarian cancer (EOC). When compared with primary human ovarian surface epithelial (pHOSE) cells, EZH2, SUZ12, and EED were expressed at higher levels in all 8 human EOC cell lines tested. Consistently, H3K27Me3 was also overexpressed in human EOC cell lines compared with pHOSE cells. EZH2 was significantly overexpressed in primary human EOCs (n = 134) when compared with normal ovarian surface epithelium (n = 46; P &lt; 0.001). EZH2 expression positively correlated with expression of Ki67 (P &lt; 0.001; a marker of cell proliferation) and tumor grade (P = 0.034) but not tumor stage (P = 0.908) in EOC. There was no correlation of EZH2 expression with overall (P = 0.3) or disease-free survival (P = 0.2) in high-grade serous histotype EOC patients (n = 98). Knockdown of EZH2 expression reduced the level of H3K27Me3 and suppressed the growth of human EOC cells both in vitro and in vivo in xenograft models. EZH2 knockdown induced apoptosis of human EOC cells. Finally, we showed that EZH2 knockdown suppressed the invasion of human EOC cells. Together, these data demonstrate that EZH2 is frequently overexpressed in human EOC cells and its overexpression promotes the proliferation and invasion of human EOC cells, suggesting that EZH2 is a potential target for developing EOC therapeutics. Mol Cancer Res; 8(12); 1610–8. ©2010 AACR.
miR-200 Inhibits Lung Adenocarcinoma Cell Invasion and Metastasis by Targeting Flt1/VEGFR1
Authors: Roybal Jonathon D. , Zang Yi , Ahn Young-Ho , Yang Yanan , Gibbons Don L. , Baird Brandi N. , Alvarez Cristina , Thilaganathan Nishan , Liu Diane D. , Saintigny Pierre , Heymach John V. , Creighton Chad J. , Kurie Jonathan M. 
Published: November 2010

Abstract
The microRNA-200 (miR-200) family is part of a gene expression signature that predicts poor prognosis in lung cancer patients. In a mouse model of K-ras/p53-mutant lung adenocarcinoma, miR-200 levels are suppressed in metastasis-prone tumor cells, and forced miR-200 expression inhibits tumor growth and metastasis, but the miR-200 target genes that drive lung tumorigenesis have not been fully elucidated. Here, we scanned the genome for putative miR-200 binding sites and found them in the 3′-untranslated region (3′-UTR) of 35 genes that are amplified in human cancer. Mining of a database of resected human lung adenocarcinomas revealed that the levels of one of these genes, Flt1/VEGFR1, correlate inversely with duration of survival. Forced miR-200 expression suppressed Flt1 levels in metastasis-prone lung adenocarcinoma cells derived from K-ras/p53-mutant mice, and negatively regulated the Flt1 3′-UTR in reporter assays. Cancer-associated fibroblasts (CAFs) isolated from murine lung adenocarcinomas secreted abundant VEGF and enhanced tumor cell invasion in coculture studies. CAF-induced tumor cell invasion was abrogated by VEGF neutralization or Flt1 knockdown in tumor cells. Flt1 knockdown decreased the growth and metastasis of tumor cells in syngeneic mice. We conclude that miR-200 suppresses lung tumorigenesis by targeting Flt1. Mol Cancer Res; 9(1); 25–35 ©2010 AACR.
Economic Evaluation of Fractional Flow Reserve–Guided Percutaneous Coronary Intervention in Patients With Multivessel Disease
Authors: Fearon William F. , Bornschein Bernhard , Tonino Pim A.L. , Gothe Raffaella M. , Bruyne Bernard De , Pijls Nico H.J. , Siebert Uwe 
Published: November 2010

Background—
The Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) study demonstrated significantly improved health outcomes at 1 year in patients randomized to multivessel percutaneous coronary intervention guided by fractional flow reserve (FFR) compared with percutaneous coronary intervention guided by angiography alone. The economic impact of routine measurement of FFR in this setting is not known.

Methods and Results—

In this study, 1005 patients were randomly assigned to FFR-guided or angiography-guided percutaneous coronary intervention and followed up for 1 year. A prospective cost-utility analysis comparing costs and quality-adjusted life-years was performed with a time horizon of 1 year. Quality-adjusted life-years were calculated with the use of utilities determined by the EuroQuol 5 dimension health survey with US weights. Direct medical costs included those of the index procedure and hospitalization and costs for major adverse cardiac events during follow-up. Confidence intervals for both quality-adjusted life-years and costs were estimated by the bootstrap percentile method. Major adverse cardiac events at 1 year occurred in 13.2% of those in the FFR-guided arm and 18.3% of those in the angiography-guided arm (
P
=0.02). Quality-adjusted life-years were slightly greater in the FFR-guided arm (0.853 versus 0.838;
P
=0.2). Mean overall costs at 1 year were significantly less in the FFR-guided arm ($14 315 versus $16 700;
P
<0.001). Bootstrap simulation indicated that the FFR-guided strategy was cost-saving in 90.74% and cost-effective at a threshold of US $50 000 per quality-adjusted life-years in 99.96%. Sensitivity analyses demonstrated robust results.

Conclusion—
Economic evaluation of the FAME study reveals that FFR-guided percutaneous coronary intervention in patients with multivessel coronary disease is one of those rare situations in which a new technology not only improves outcomes but also saves resources.

Clinical Trial Registration—

URL:
http://ClinicalTrials.gov
. Unique identifier: NCT00267774.
Influence of Age on Associations Between Childhood Risk Factors and Carotid Intima-Media Thickness in Adulthood
Authors: Juonala Markus , Magnussen Costan G. , Venn Alison , Dwyer Terence , Burns Trudy L. , Davis Patricia H. , Chen Wei , Srinivasan Sathanur R. , Daniels Stephen R. , Kähönen Mika , Laitinen Tomi , Taittonen Leena , Berenson Gerald S. , Viikari Jorma S.A. , Raitakari Olli T. 
Published: November 2010

Background—
Atherosclerosis has its roots in childhood. Therefore, defining the age when childhood risk exposure begins to relate to adult atherosclerosis may have implications for pediatric cardiovascular disease prevention and provide insights about the early determinants of atherosclerosis development. The aim of this study was to investigate the influence of age on the associations between childhood risk factors and carotid artery intima-media thickness, a marker of subclinical atherosclerosis.

Methods and Results—

We used data for 4380 members of 4 prospective cohorts—Cardiovascular Risk in Young Finns Study (Finland), Childhood Determinants of Adult Health study (Australia), Bogalusa Heart Study (United States), and Muscatine Study (United States)—that have collected cardiovascular risk factor data from childhood (age 3 to 18 years) and performed intima-media thickness measurements in adulthood (age 20 to 45 years). The number of childhood risk factors (high [highest quintile] total cholesterol, triglycerides, blood pressure, and body mass index) was predictive of elevated intima-media thickness (highest decile) on the basis of risk factors measured at age 9 years (odds ratio [95% confidence interval] 1.37 [1.16 to 1.61],
P
=0.0003), 12 years (1.48 [1.28 to 1.72],
P
<0.0001), 15 years (1.56 [1.36 to 1.78],
P
<0.0001), and 18 years (1.57 [1.31 to 1.87],
P
<0.0001). The associations with risk factors measured at age 3 years (1.17 [0.80 to 1.71],
P
=0.42) and 6 years (1.20 [0.96 to 1.51],
P
=0.13) were weaker and nonsignificant.

Conclusions—
Our analyses from 4 longitudinal cohorts showed that the strength of the associations between childhood risk factors and carotid intima-media thickness is dependent on childhood age. On the basis of these data, risk factor measurements obtained at or after 9 years of age are predictive of subclinical atherosclerosis in adulthood.
Migraine and Functional Outcome From Ischemic Cerebral Events in Women
Authors: Rist Pamela M. , Buring Julie E. , Kase Carlos S. , Schürks Markus , Kurth Tobias 
Published: November 2010

Background—
Studies have linked migraine with aura to an increased risk of ischemic stroke, particularly among women. Data on the relationship of migraine and functional outcome from ischemic cerebral events are sparse.

Methods and Results—
This was a prospective cohort study among 27 852 women enrolled in the Women's Health Study for whom we had information on migraine and measured cholesterol values and who had no prior stroke or transient ischemic attack (TIA) at baseline. Migraine was classified into no history of migraine, active migraine with aura, active migraine without aura, and past history of migraine. Possible functional outcomes were no stroke or TIA, TIA, and stroke with modified Rankin Scale (mRS) score 0 to 1, mRS 2 to 3, and mRS 4 to 6. We used multinomial logistic regression to evaluate the relationship of migraine with functional outcomes after ischemic stroke. During a mean of 13.5 years of follow-up, 398 TIAs and 345 ischemic strokes occurred. Compared with women without history of migraine and who did not experience a TIA or stroke, women who reported migraine with aura had adjusted relative risk (95% confidence interval) of 1.56 (1.03 to 2.36) for TIA, 2.33 (1.37 to 3.97) for stroke with mRS 0 to 1, 0.82 (0.30 to 2.24) for mRS 2 to 3, and 1.18 (0.28 to 4.97) for mRS 4 to 6. The risk of any outcome was not significantly elevated for women who experienced migraine without aura or who had a past history of migraine.

Conclusions—
Results of this large prospective cohort suggest that women with migraine with aura are at increased risk of experiencing TIA or ischemic stroke with good functional outcome.
Cyclone Interactions and Evolutions during the “Perfect Storms” of Late October and Early November 1991
Authors: Cordeira Jason M. , Bosart Lance F. 
Published: November 2010

Abstract
This paper examines the cyclogenesis of the “Perfect Storms” of late October and early November 1991 over the North Atlantic and focuses on the influence of Hurricane Grace (HG) toward their development. The two storms considered are the “Perfect Storm” (PS) that underwent a warm seclusion process and an extratropical cyclone (EC1) with two development phases. HG, which initially formed via tropical transition (TT), influenced the first phase of EC1 via reduced atmospheric static stability and enhanced low-level baroclinicity. As a result, deep moist convection and latent heat release produced maxima in midtropospheric diabatic heating and lower-tropospheric potential vorticity (PV) that aided the development of EC1. Backward air parcel trajectories and large diabatic contributions to eddy available potential energy (APE) generation suggests that EC1 developed as a diabatic Rossby vortex (DRV)-like feature.
The second and explosively deepening phase of EC1 occurred as the cyclone coupled with an upper-tropospheric PV disturbance (PVD) over the eastern North Atlantic. Backward air parcel trajectories demonstrate the explosive deepening of EC1 involved airstreams originating from east of HG and from over the Labrador Sea. Parcel trajectories and a large baroclinic contribution to eddy APE generation further suggests that the two-phase development of EC1 may have involved a DRV-like feature.
The subsequent recurvature and extratropical transition (ET) of HG occurred in the warm sector of the PS downstream of a second upper-tropospheric PVD over the western North Atlantic. Reduced atmospheric static stability, enhanced warm air advection, and strong latent heat release during the recurvature and ET of HG contributed to the development of a strong, zonally oriented warm front and the warm seclusion of the PS. Parcel trajectory analysis demonstrates that the PS warm seclusion involved the isolation of air parcels by a bent-back warm front that were warmed via sensible heating from the underlying Gulf Stream.
Genome-wide DNA profiling of marginal zone lymphomas identifies subtype-specific lesions with an impact on the clinical outcome
Authors: Rinaldi Andrea , Mian Michael , Chigrinova Ekaterina , Arcaini Luca , Bhagat Govind , Novak Urban , Rancoita Paola M. V. , De Campos Cassio P. , Forconi Francesco , Gascoyne Randy D. , Facchetti Fabio , Ponzoni Maurilio , Govi Silvia , Ferreri Andrés J. M. , Mollejo Manuela , Piris Miguel A. , Baldini Luca , Soulier Jean , Thieblemont Catherine , Canzonieri Vincenzo , Gattei Valter , Marasca Roberto , Franceschetti Silvia , Gaidano Gianluca , Tucci Alessandra , Uccella Silvia , Tibiletti Maria Grazia , Dirnhofer Stephan , Tripodo Claudio , Doglioni Claudio , Dalla Favera Riccardo , Cavalli Franco , Zucca Emanuele , Kwee Ivo , Bertoni Francesco 
Published: November 2010

AbstractMarginal zone B-cell lymphomas (MZLs) have been divided into 3 distinct subtypes (extranodal MZLs of mucosa-associated lymphoid tissue [MALT] type, nodal MZLs, and splenic MZLs). Nevertheless, the relationship between the subtypes is still unclear. We performed a comprehensive analysis of genomic DNA copy number changes in a very large series of MZL cases with the aim of addressing this question. Samples from 218 MZL patients (25 nodal, 57 MALT, 134 splenic, and 2 not better specified MZLs) were analyzed with the Affymetrix Human Mapping 250K SNP arrays, and the data combined with matched gene expression in 33 of 218 cases. MALT lymphoma presented significantly more frequently gains at 3p, 6p, 18p, and del(6q23) (TNFAIP3/A20), whereas splenic MZLs was associated with del(7q31), del(8p). Nodal MZLs did not show statistically significant differences compared with MALT lymphoma while lacking the splenic MZLs-related 7q losses. Gains of 3q and 18q were common to all 3 subtypes. del(8p) was often present together with del(17p) (TP53). Although del(17p) did not determine a worse outcome and del(8p) was only of borderline significance, the presence of both deletions had a highly significant negative impact on the outcome of splenic MZLs.