bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of the HefC Efflux Pump inHelicobacter pyloriCholesterol-Dependent Resistance to Ceragenins and Bile Salts
Authors: Trainor Elizabeth A. , Horton Katherine E. , Savage Paul B. , Testerman Traci L. , McGee David J. 
Published: October 2010

ABSTRACTThe human gastric pathogenHelicobacter pylorimodifies host cholesterol via glycosylation and incorporates the glycosylated cholesterol into its membrane; however, the benefits of cholesterol toH. pyloriare largely unknown. We speculated that cholesterol in theH. pylorimembrane might alter the susceptibility of these organisms to membrane-disrupting antibacterial compounds. To test this hypothesis,H. pyloristrains were cultured in Ham's F-12 chemically defined medium in the presence or absence of cholesterol. The two cultures were subjected to overnight incubations with serial 2-fold dilutions of 10 bile salts and four ceragenins, which are novel bile salt derivatives that mimic membrane-disrupting activity of antimicrobial peptides.H. pyloricultured with cholesterol was substantially more resistant to seven of the bile salts and three ceragenins thanH. pyloricultured without cholesterol. In most cases, these cholesterol-dependent differences ranged from 2 to 7 orders of magnitude; this magnitude depended on concentration of the agent. Cholesterol is modified by glycosylation using Cgt, a cholesteryl glycosyltransferase. Surprisingly, acgtknockout strain still maintained cholesterol-dependent resistance to bile salts and ceragenins, indicating that cholesterol modification was not involved in resistance. We then tested whether three putative, paralogous inner membrane efflux pumps, HefC, HefF, or HefI, played a role. While HefF and HefI appeared unimportant, HefC was shown to play a critical role in the resistance to bile salts and ceragenins by multiple methods in multiple strain backgrounds. Thus, both cholesterol and the putative bile salt efflux pump HefC play important roles inH. pyloriresistance to bile salts and ceragenins.
Infectivity Acts asIn VivoSelection for Maintenance of the Chlamydial Cryptic Plasmid
Authors: Russell Marsha , Darville Toni , Chandra-Kuntal Kumar , Smith Bennett , Andrews Charles W. , O'Connell Catherine M. 
Published: October 2010

ABSTRACTChlamydia trachomatiscontains a conserved ∼7.5-kb plasmid. Loss of the plasmid results in reduced glycogen accumulation, failure to activate TLR2, and reduced infectivity. We hypothesized that reduced infectivity functions as a means of selection for plasmid maintenance. We directly examined the biological significance of the reduced infectivity associated with plasmid deficiency by determining the relative fitness of plasmid-deficient CM972 versus that of wild-typeC. muridarumNigg in mixed inoculain vitroandin vivo.C. muridarumNigg rapidly out-competed its plasmid-cured derivative CM972in vitrobut was not competitive with CM3.1, a derivative of CM972 that has reverted to a normal infectivity phenotype.C. muridarumNigg also effectively competed with CM972 during lower and upper genital tract infection in the mouse, demonstrating that strong selective pressure for plasmid maintenance occurs during infection. The severity of oviduct inflammation and dilatation resulting from these mixed infections correlated directly with the amount ofC. muridarumNigg in the initial inoculum, confirming the role of the plasmid in virulence. Genetic characterization of CM972 and CM3.1 revealed no additional mutations (other than loss of the plasmid) to account for the reduced infectivity of CM972 and detected a single base substitution in TC_0236 in CM3.1 that may be responsible for its restored infectivity. These data demonstrate that a chlamydial strain that differs genetically from its wild-type parent only with respect to the lack of the chlamydial plasmid is unable to competein vitroandin vivo, likely explaining the rarity of plasmid-deficient isolates in nature.
Associations of low-level urine cadmium with kidney function in lead workers
Authors: Weaver Virginia M , Kim Nam-Soo , Jaar Bernard G , Schwartz Brian S , Parsons Patrick J , Steuerwald Amy J , Todd Andrew C , Simon David , Lee Byung-Kook 
Published: October 2010

ObjectivesLow-level cadmium exposure, resulting in, for example, urinary cadmium <2.0 μg/g creatinine, is widespread; recent data suggest nephrotoxicity even at these low levels. Few studies have examined the impact of low-level cadmium exposure in workers who are occupationally exposed to other nephrotoxicants such as lead.MethodsWe evaluated associations of urine cadmium, a measure of cumulative dose, with four glomerular filtration measures and N-acetyl-β-D-glucosaminidase (NAG) in lead workers. Recent and cumulative lead doses were assessed via blood and tibia lead, respectively.ResultsIn 712 lead workers, mean (SD) blood and tibia lead values, urine cadmium values and estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease equation were 23.1 (14.1) μg/dl, 26.6 (28.9) μg Pb/g bone mineral, 1.15 (0.66) μg/g creatinine and 97.4 (19.2) ml/min/1.73 m2, respectively. After adjustment for age, sex, body mass index, urine creatinine, smoking, alcohol, education, annual income, diastolic blood pressure, current or former lead worker job status, new or returning study participant, and blood and tibia lead, higher ln-urine cadmium was associated with higher calculated creatinine clearance, eGFR (β=8.7 ml/min/1.73 m2; 95% CI 5.4 to 12.1) and ln-NAG but lower serum creatinine.ConclusionsPotential explanations for these results include a normal physiological response in which urine cadmium levels reflect renal filtration, the impact of adjustment for urine dilution with creatinine in models of kidney outcomes, and cadmium-related hyperfiltration.
Genotypic Profiling of 452 Choroidal Melanomas with Multiplex Ligation-Dependent Probe Amplification
Authors: Damato Bertil , Dopierala Justyna A. , Coupland Sarah E. 
Published: October 2010

Abstract
Purpose: Metastasis from uveal melanoma occurs almost exclusively with tumors showing chromosome 3 loss. We used multiplex ligation-dependent probe amplification (MLPA) to detect chromosome 1p, 3, 6p, 6q, 8p, and 8q abnormalities in uveal melanomas. The purpose of this study was to correlate our MLPA results with other risk factors and metastatic death.
Experimental Design: Patients were included if they had a uveal melanoma involving choroid. Correlations between baseline risk factors were analyzed using the chi-square test (without Yates's adjustment) and the Mann–Whitney test, with log-rank analysis for associations with metastatic death.
Results: The patients (194 female; 258 male) had a median age of 59.4 years and a median follow-up of 1.89 years. MLPA abnormalities occurred in a wide variety of combinations. Ten-year disease-specific mortality was 0% in 133 tumors with no chromosome 3 loss, 55% in tumors with chromosome 3 loss but no chromosome 8q gain, and 71% in 168 tumors showing combined chromosome 3 loss and 8q gain. In tumors with both these abnormalities, epithelioid melanoma cytomorphology, closed loops, and high mitotic rate correlated with poor survival as did lack of chromosome 6p gain.
Conclusions: These results support the use of MLPA for routine clinical prognostication, especially if the genetic data are considered together with clinical and histologic risk factors. We showed a wide variety of MLPA results, which suggests that chromosomal abnormalities in uveal melanoma accumulate in a variable sequence.
Clinical Correlates of NRAS and BRAF Mutations in Primary Human Melanoma
Authors: Ellerhorst Julie A. , Greene Victoria R. , Ekmekcioglu Suhendan , Warneke Carla L. , Johnson Marcella M. , Cooke Carolyn P. , Wang Li-E , Prieto Victor G. , Gershenwald Jeffrey E. , Wei Qingyi , Grimm Elizabeth A. 
Published: October 2010

Abstract
Purpose: NRAS and BRAF mutations are common in cutaneous melanomas, although rarely detected mutually in the same tumor. Distinct clinical correlates of these mutations have not been described, despite in vitro data suggesting enhanced oncogenic effects. This study was designed to test the hypothesis that primary human cutaneous melanomas harboring mutations in NRAS or BRAF display a more aggressive clinical phenotype than tumors wild type at both loci.
Experimental Design: Microdissection of 223 primary melanomas was carried out, followed by determination of the NRAS and BRAF mutational status. Genotypic findings were correlated with features known to influence tumor behavior including age, gender, Breslow depth, Clark level, mitotic rate, the presence of ulceration, and American Joint Committee on Cancer (AJCC) staging.
Results: Breslow depth and Clark level varied significantly among the genotypes, with NRAS mutants showing the deepest levels and wild-type tumors the least depth. Ulceration also differed significantly among the genotypes, with BRAF mutants demonstrating the highest rate. In addition, tumors with mutated NRAS were more likely to be located on the extremities. Patients whose tumors carried either mutation presented with more advanced AJCC stages compared with patients with wild-type tumors, and specifically, were more likely to have stage III disease at diagnosis. Overall survival did not differ among the 3 groups.
Conclusions: Distinct clinical phenotypes exist for melanomas bearing NRAS and BRAF mutations, whether considered together or separately, and are associated with features known to predict aggressive tumor behavior. The impact of these mutations is most evident at earlier stages of disease progression. Clin Cancer Res; 17(2); 229–35. ©2010 AACR. Clin Cancer Res; 17(2); 229–35. ©2010 AACR.
Hospital Outcome of Moderate to Severe Pericardial Effusion Complicating ST-Elevation Acute Myocardial Infarction
Authors: Figueras Jaume , Barrabés José A. , Serra Vicens , Cortadellas Josefa , Lidón Rosa-Maria , Carrizo Alvaro , Garcia-Dorado David 
Published: October 2010

Background—
Hospital prognosis of moderate to severe pericardial effusion (MPE; ≥10 mm) in ST-elevation myocardial infarction is largely unknown.

Methods and Results—

Data from 446 ST-elevation myocardial infarction patients, 228 with MPE—88 with cardiac tamponade (CT) and electromechanical dissociation (EMD), 44 with CT without EMD (w/oEMD), and 96 without initial CT—and 218 with small PE (5 to 9 mm), were compared. Patients with MPE without initial CT were also compared with 96 patients without PE. CT patients showed larger PE (
P
<0.001) than those without initial CT; 85% of those with CT+EMD and 86% with CTw/oEMD were treated with pericardiocentesis and 10% and 21% were treated with a surgical repair, respectively. Among MPE patients, 30-day mortality was 43% and was higher in those with CT+EMD (operated, 89%; and nonoperated, 85%) than in those with CTw/oEMD (22% and 11%, respectively;
P
<0.001) and those without initial CT (17%;
P
<0.001). It was also higher than in patients with small PE (10%;
P
<0.001) or those without PE (6%;
P
=0.001). Death was attributable to cardiac rupture in 83% of patients with CT+EMD, 7% with CTw/oEMD, and 8% with MPE without initial CT and occurred late (≥7 days) in 14%, 67%, and 100%, respectively.

Conclusions—
MPE carries an increased mortality that is highest in patients with CT+EMD. In those with CTw/oEMD, however, mortality is considerably low after pericardiocentesis, and subsequent management may be individualized because a conservative approach is often successful. Importantly, MPE patients without initial CT are not free from late rupture and deserve further investigation.
Relationship of Echocardiographic Dyssynchrony to Long-Term Survival After Cardiac Resynchronization Therapy
Authors: Gorcsan John , Oyenuga Olusegun , Habib Phillip J. , Tanaka Hidekazu , Adelstein Evan C. , Hara Hideyuki , McNamara Dennis M. , Saba Samir 
Published: October 2010

Background—
The ability of echocardiographic dyssynchrony to predict response to cardiac resynchronization therapy (CRT) has been unclear.

Methods and Results—

A prospective, longitudinal study was designed with predefined dyssynchrony indexes and outcome variables to test the hypothesis that baseline dyssynchrony is associated with long-term survival after CRT. We studied 229 consecutive class III to IV heart failure patients with ejection fraction ≤35 and QRS duration ≥120 milliseconds for CRT. Dyssynchrony before CRT was defined as tissue Doppler velocity opposing-wall delay ≥65 milliseconds, 12-site SD (Yu Index) ≥32 milliseconds, speckle tracking radial strain anteroseptal-to-posterior wall delay ≥130 milliseconds, or pulsed Doppler interventricular mechanical delay ≥40 milliseconds. Outcome was defined as freedom from death, heart transplantation, or left ventricular assist device implantation. Of 210 patients (89) with dyssynchrony data available, there were 62 events: 47 deaths, 9 transplantations, and 6 left ventricular assist device implantations over 4 years. Event-free survival was associated with Yu Index (
P
=0.003), speckle tracking radial strain (
P
=0.003), and interventricular mechanical delay (
P
=0.019). When adjusted for confounding baseline variables of ischemic origin and QRS duration, Yu Index and radial strain dyssynchrony remained independently associated with outcome (
P
<0.05). Lack of radial dyssynchrony was particularly associated with unfavorable outcome in those with QRS duration of 120 to 150 milliseconds (
P
=0.002).

Conclusions—
The absence of echocardiographic dyssynchrony was associated with significantly less favorable event-free survival after CRT. Patients with narrower QRS duration who lacked dyssynchrony had the least favorable long-term outcome. These observations support the relationship of dyssynchrony and CRT response.
Effects of HIV Protease Inhibitors on Progression of Monocrotaline- and Hypoxia-Induced Pulmonary Hypertension in Rats
Authors: Gary-Bobo Guillaume , Houssaini Amal , Amsellem Valerie , Rideau Dominique , Pacaud Pierre , Perrin Aline , Brégeon Jérémy , Marcos Elisabeth , Dubois-Randé Jean-Luc , Sitbon Olivier , Savale Laurent , Adnot Serge 
Published: October 2010

Background—
Pulmonary hypertension (PH) is among the complications of HIV infection. Combination antiretroviral therapy may influence the progression of HIV-related PH. Because Akt signaling is a potential molecular target of HIV protease inhibitors (HPIs), we hypothesized that these drugs altered monocrotaline- and hypoxia-induced PH in rats by downregulating the Akt pathway, thereby inhibiting pulmonary artery smooth muscle cell proliferation.

Methods and Results—
Daily treatment with each of 3 first-generation HPIs (ritonavir 30 mg/kg, amprenavir 100 mg/kg, and nelfinavir 500 mg/kg) started 3 weeks after a subcutaneous monocrotaline injection (60 mg/kg) substantially diminished pulmonary artery pressure, right ventricular hypertrophy, number of muscularized pulmonary vessels, pulmonary arterial wall thickness, and proliferating pulmonary vascular Ki67-labeled cells without affecting vessel caspase 3 staining. HPI treatment partially prevented the development of hypoxia- and monocrotaline-induced PH. Monocrotaline-induced PH was associated with marked activation of Akt signaling in the lungs and proximal pulmonary arteries, with increases in phosphorylated Akt, phosphorylated glycogen-synthase-kinase-3β (GSK3), and phosphorylated endothelial nitric oxide synthase, all of which decreased markedly after treatment with each HPI. In contrast, PH-associated increases in phosphorylated extracellular signal-related kinase 1/2 and myosin light-chain phosphatase were unaltered by the HPIs. The 3 HPIs and the phosphatidylinositol 3-kinase inhibitor LY294002 inhibited platelet-derived growth factor–induced phosphorylation of Akt and GSK3 in cultured pulmonary artery smooth muscle cells and blocked cell proliferation; this last effect was abolished by the GSK3 inhibitor SB216763.

Conclusion—
These results support an effect of HPIs on pulmonary vascular remodeling mediated by inhibition of Akt phosphorylation and consequently of pulmonary artery smooth muscle cell proliferation.
The Vertical Structures of Atmospheric Temperature Anomalies Associated with Two Flavors of El Niño Simulated by AMIP II Models
Authors: Zhou Tianjun , Zhang Jie 
Published: October 2010

Abstract
Recent studies have identified different modes associated with two flavors of El Niño in terms of the three-dimensional structure of atmospheric temperature. The first is a deep-warm mode, which features a coherent zonal mean warming throughout the troposphere from 30°N to 30°S with cooling aloft. The second is a shallow-warm mode, which features strong wave signatures in the troposphere with warmth (coolness) over the central Pacific (western Pacific). The ability to simulate these two modes is a useful metric for evaluating climate models. To understand the reproducibility of these two modes, the authors analyzed the multimodel ensemble mean (MMEM) of 11 atmospheric general circulation models (AGCMs) that participated in the second phase of the Atmospheric Model Intercomparison Project (AMIP II). Each model was run in an AGCM-alone mode forced by historical sea surface temperatures covering the period 1980–99. The authors find that atmospheric temperature variability is generally well captured in the MMEM of AMIP II models, demonstrating that the observational changes documented here are driven by SST changes during the El Niño events and the variety of vertical temperature structures associated with two flavors of El Niño are highly reproducible. The model skill for the first mode is slightly higher than the second mode. The skill in the upper troposphere–lower stratosphere is lower than for the tropospheric counterpart, especially at high latitudes. The performances of individual models are also assessed. The authors also show some differences from previous data analyses, including the variance accounted for by the two modes, as well as the lead–lag relationship of the shallow-warm mode with the Niño-3.4 index.
Time Scales of Variability of the Tropical Atmosphere Derived from Cloud-Defined Weather States
Authors: Tselioudis George , Rossow William B. 
Published: October 2010

Abstract
The recent analysis of Rossow et al. used a clustering technique to derive six tropical weather states (WS) based on mesoscale cloud-type patterns and documented the spatial distribution of those WS and the modes of variability of the convective WS in the tropical western Pacific. In this study, the global tropics are separated into 30° × 30° regions, and a clustering algorithm is applied to the regional WS frequency distributions to derive the dominant modes of weather state variability (or the climate state variability) in each region. The results show that the whole tropical atmosphere oscillates between a convectively active and a convectively suppressed regime with the exception of the eastern parts of the two ocean basins, where the oscillation is between a stratocumulus and a trade cumulus regime. The dominant mode of both those oscillations is the seasonal cycle with the exception of the eastern Indian and western–central Pacific region, where El Niño frequencies dominate. The transitions between the convectively active and suppressed regimes produce longwave (LW) and shortwave (SW) top-of-atmosphere (TOA) radiative differences that are of opposite sign and of similar magnitude, being of order 20–30 W m−2 over ocean and 10–20 W m−2 over land and thus producing an overall balance in the TOA radiative budget. The precipitation differences between the convectively active and suppressed regimes are found to be of order 2.5–3 mm day−1 over ocean and 1–2.4 mm day−1 over land. Finally, the transitions between the stratocumulus and shallow cumulus regimes produce noticeable TOA SW differences of order 10–20 W m−2 and very small TOA LW and precipitation differences. The potential climate feedback implications of the regime radiation and precipitation differences are discussed.
Tropical Indian Ocean Influence on Northwest Pacific Tropical Cyclones in Summer following Strong El Niño*
Authors: Du Yan , Yang Lei , Xie Shang-Ping 
Published: October 2010

Abstract
In the summer following a strong El Niño, tropical cyclone (TC) number decreases over the Northwest (NW) Pacific despite little change in local sea surface temperature. The authors’ analysis suggests El Niño–induced tropical Indian Ocean (TIO) warming as the cause. The TIO warming forces a warm tropospheric Kelvin wave that propagates into the western Pacific. Inducing surface divergence off the equator, the tropospheric Kelvin wave suppresses convection and induces an anomalous anticyclone over the NW Pacific, both anomalies unfavorable for TCs. The westerly vertical shear associated with the warm Kelvin wave reduces the magnitude of vertical shear in the South China Sea and strengthens it in the NW Pacific, an east–west variation that causes TC activity to increase and decrease in respective regions. These results help improve seasonal TC prediction.
Feminism, Gender studies, and Medieval Studies
Authors: Caviness Madeline H. 
Published: October 2010

AbstractThis article traces the multiple and rapid changes that have occurred during the past fifteen years, in theorizing “sex/gender arrangements”. A secondary aspect is the reception, application and above all modification of these theories by some scholars of European medieval cultural production, in which varieties of difference are found that do not apply in modern societies. Deconstruction of the binary m/f (whether thought of as sexual or gender difference) erupted among feminist thinkers in the 1990s and eventually “queered” academic discourses by destabilizing labels that had been naturalized, including a consistent gender identity for the individual in medieval or modern society. The author claims that queer and post-colonial theory, far from being antithetical to feminist theory, are out-growths of it, and exist in parallel; the proponents of each are concerned with the societal forces, including our own discourses, that maintain difference, and create communities of oppression Yet it is also necessary to raise the question, when will the next radical departure occur, and how will new theories be generated?
Between Poiesis and Praxis: Women and Art
Authors: Collin Françoise 
Published: October 2010

AbstractIf we think of artistic creation as a basic dimension of humanity we need to question the absence of female artists in history. We should also look at their gradual emergence in the late 20th century, an emergence that coincides with the feminist movement and a change in the conception of art itself, revealed chiefly by Duchamp.But does art by women have some specificity? Without giving a definite answer as far as subject matter is concerned, we note that the conditions suited to both history and the history of art may affect their creation but without specifying it ontologically. If, moreover, some women artists define their work as feminist, it is through an act that combines artistic and political transgression. The exhibition currently arranged by the Georges Pompidou Centre, elles@beaubourg, provides new resources for these complex questions.
Bio-Technosciences in Philosophy: Challenges and Perspectives for Gender Studies in Philosophy
Authors: Lettow Susanne 
Published: October 2010

AbstractSince the 1960s the bio/technosciences have occupied a central place in philosophical thinking. The paper sets out three theoretical configurations embodying major challenges for today's gender studies in philosophy, since they raise an obstacle, each in its own way, to the discussion on implications of the bio/technosciences in the political field and the area of gender theory: firstly naturalism in the field of the philosophy of science; secondly the paradigm of applied ethics; and thirdly the discourse of philosophical anthropology that has been reactivated in philosophical debates about the bio/technosciences. To conclude, some of the future tasks will be mentioned which fall to gender studies in philosophy.