bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Staphylococcus aureus Two-Component Regulatory System, GraRS, Senses and Confers Resistance to Selected Cationic Antimicrobial Peptides
Authors: Yang Soo-Jin , Bayer Arnold S. , Mishra Nagendra N. , Meehl Michael , Ledala Nagender , Yeaman Michael R. , Xiong Yan Q. , Cheung Ambrose L. 
Published: October 2011

ABSTRACT

The two-component regulatory system, GraRS, appears to be involved in staphylococcal responses to cationic antimicrobial peptides (CAPs). However, the mechanism(s) by which GraRS is induced, regulated, and modulated remain undefined. In this study, we used two well-characterized MRSA strains (Mu50 and COL) and their respective mutants of
graR
and
vraG
(encoding the ABC transporter-dependent efflux pump immediately downstream of
graRS
), and show that (i) the expression of two key determinants of net positive surface charge (
mprF
and
dlt
) is dependent on the cotranscription of both
graR
and
vraG
, (ii) reduced expression of
mprF
and
dlt
in
graR
mutants was phenotypically associated with reduced surface-positive charge, (iii) this net reduction in surface-positive charge in
graR
and
vraG
mutants, in turn, correlated with enhanced killing by a range of CAPs of diverse structure and origin, including those from mammalian platelets (tPMPs) and neutrophils (hNP-1) and from bacteria (polymyxin B), and (iv) the synthesis and translocation of membrane lysyl-phosphatidylglycerol (an
mprF
-dependent function) was substantially lower in
graR
and
vraG
mutants than in parental strains. Importantly, the inducibility of
mprF
and
dlt
transcription via the
graRS-vraFG
pathway was selective, with induction by sublethal exposure to the CAPs, RP-1 (platelets), and polymyxin B, but not by other cationic molecules (hNP-1, vancomycin, gentamicin, or calcium-daptomycin). Although
graR
regulates expression of
vraG
, the expression of
graR
was codependent on an intact downstream
vraG
locus. Collectively, these data support an important role of the
graRS
and
vraFG
loci in the sensing of and response to specific CAPs involved in innate host defenses.
Photosynthetic production of ground vegetation in different-aged Scots pine (Pinus sylvestris) forests
Authors: Kulmala L. , Pumpanen J. , Kolari P. , Muukkonen P. , Hari P. , Vesala T. 
Published: October 2011

The photosynthesis of ground vegetation is dependent on species composition and environmental factors that are extremely diverse during forest succession. However, present in situ measurements over the gross primary production (GPP) of ground vegetation are unable to cover this variability. The primary objective of the present study was to estimate the GPP of ground vegetation in five differently aged Scots pine (Pinus sylvestris L.) forests in southern Finland during the growing season of 2006 by using temperature, soil moisture, photosynthetically active radiation, and biomass of the ground vegetation to run a known process-based model. The GPP of ground vegetation was ~350 g·m–2 at the 6- and 12-year-old sites and 168, 146, and 41 g·m–2 thereafter at the 20-, 45-, and 120-year-old sites, respectively. The values decreased with stand age, because as the stand ages, light availability decreases, the dominant species below the canopy show lower rates of photosynthesis than species in open areas, and the biomass of the ground vegetation decreases. Grasses and herbs took up nearly half of the value at the youngest site but their role decreased thereafter, whereas low shrubs were responsible for most of the GPP of ground vegetation below closed canopies.
Ranking of four contributions to error in stand-level Douglas-fir log supply and value recovery estimation
Authors: Murphy Glen E. , Acuna Mauricio A. 
Published: October 2011

Sustainability and globally competitive forest product supply markets are two of the pressures that forest managers face today. Both require that managers have good metrics of the quantity, quality, and location of timber resources within their forests. The value of this information must be weighed against the cost of obtaining it and losses associated with not having access to it. A cost-plus-loss procedure for assessing the relative contributions to error in estimating stand-level value recovery and log product yields was developed and tested on two Douglas-fir ( Pseudotsuga menziesii (Mirb.) Franco) stands in Oregon. The sources of error were those associated with (i) market complexity, (ii) sampling intensity, (iii) stem quality assessment methods, and (iv) bucking optimization algorithms. Two performance measures were used as part of the assessment procedure: market fulfilment and the difference in total net value recovery between having complete and less than complete information. Average market fulfilment ranged between 60% and 100%. The difference in total net value recovery ranged from –21.2% to +0.8%. Stem quality assessment followed by bucking optimization algorithms and sampling intensity had the greatest effects on these performance measures. Market complexity had a negligible effect on these performance measures but affected net value recovery.
Targeting PI3K/mTOR Signaling in Cancer
Authors: Emerling Brooke M. , Akcakanat Argun 
Published: October 2011

Abstract
The American Association for Cancer Research (AACR) Special Conference on Targeting PI3K/mTOR Signaling in Cancer was held in San Francisco, California from February 24 to 27, 2011. The meeting was cochaired by Drs. Lewis C. Cantley, David M. Sabatini, and Funda Meric-Bernstam. The main focus of this event was the therapeutic potential of drugs targeting the PI3K/mTOR signaling pathway for the treatment of cancer. This article summarizes the recent discoveries in the field, with particular emphasis on the major themes of the conference. Cancer Res; 71(24); 7351–9. ©2011 AACR.
Clusterin Is a Critical Downstream Mediator of Stress-Induced YB-1 Transactivation in Prostate Cancer
Authors: Shiota Masaki , Zoubeidi Amina , Kumano Masafumi , Beraldi Eliana , Naito Seiji , Nelson Colleen C. , Sorensen Poul H.B. , Gleave Martin E. 
Published: October 2011

AbstractClusterin is a stress-activated, cytoprotective chaperone that confers broad-spectrum treatment resistance in cancer. However, the molecular mechanisms mediating CLU transcription following anticancer treatment stress remain incompletely defined. We report that Y-box binding protein-1 (YB-1) directly binds to CLU promoter regions to transcriptionally regulate clusterin expression. In response to endoplasmic reticulum stress inducers, including paclitaxel, YB-1 is translocated to the nucleus to transactivate clusterin. Furthermore, higher levels of activated YB-1 and clusterin are seen in taxane-resistant, compared with parental, prostate cancer cells. Knockdown of either YB-1 or clusterin sensitized prostate cancer cells to paclitaxel, whereas their overexpression increased resistance to taxane. Clusterin overexpression rescued cells from increased paclitaxel-induced apoptosis following YB-1 knockdown; in contrast, however, YB-1 overexpression did not rescue cells from increased paclitaxel-induced apoptosis following clusterin knockdown. Collectively, these data indicate that YB-1 transactivation of clusterin in response to stress is a critical mediator of paclitaxel resistance in prostate cancer. Mol Cancer Res; 9(12); 1755–66. ©2011 AACR.
Durable Complete Response of Metastatic Gastric Cancer with Anti-Met Therapy Followed by Resistance at Recurrence
Authors: Catenacci Daniel V. T. , Henderson Les , Xiao Shu-Yuan , Patel Premal , Yauch Robert L. , Hegde Priti , Zha Jiping , Pandita Ajay , Peterson Amy , Salgia Ravi 
Published: October 2011

AbstractA 48-year-old woman with chemorefractory metastatic gastric cancer to the liver was treated in a phase I clinical trial with MetMAb, a monoclonal antibody targeting the Met tyrosine kinase receptor. The primary tumor had high MET gene polysomy and evidence for an autocrine production of hepatocyte growth factor, the growth factor ligand of Met. A complete response was obtained that lasted 2 years; the cancer recurred as a peritoneal deposit invading into the transverse colon and a gastrohepatic ligament node. Compassionate use of MetMAb therapy at recurrence achieved a mixed response: a partial response of the two initial lesions but with development of multiple new foci of carcinomatosis. Tissue and serum studies to evaluate the Met signaling pathway correlated with MetMAb treatment response initially and at the time of recurrence.Significance: This research brief is the first to describe a durable complete response obtained with a molecularly targeted monoclonal antibody, MetMAb, to the receptor tyrosine kinase, Met, in a patient with chemorefractory metastatic gastric cancer. It is also the first to report biomarkers that predicted therapeutic response to Met inhibition. Cancer Discovery; 1(7); OF1–OF7. ©2011 AACR.Read the Commentary on this article by Feng and Ma, p. 550This article is highlighted in the In This Issue feature, p. 539
Surgery in Adults With Congenital Heart Disease
Authors: Zomer A.C. , Verheugt C.L. , Vaartjes I. , Uiterwaal C.S.P.M. , Langemeijer M.M. , Koolbergen D.R. , Hazekamp M.G. , van Melle J.P. , Konings T.C. , Bellersen L. , Grobbee D.E. , Mulder B.J.M. 
Published: October 2011

Background—
A significant proportion of patients with congenital heart disease require surgery in adulthood. We aimed to give an overview of the prevalence, distribution, and outcome of cardiovascular surgery for congenital heart disease. We specifically questioned whether the effects of surgical treatment on subsequent long-term survival depend on sex.

Methods and Results—
From the Dutch Congenital Corvitia (CONCOR) registry for adults with congenital heart disease, we identified 10 300 patients; their median age was 33.1 years. Logistic and Cox regression models were used to assess the association of surgery in adulthood with sex and with long-term survival. In total, 2015 patients (20%) underwent surgery for congenital heart disease in adulthood during a median follow-up period of 15.1 years; in 812 patients (40%), it was a reoperation. Overall, both first operations and reoperations in adulthood were performed significantly more often in men compared with women (adjusted odds ratio=1.4 [95% confidence interval, 1.2–1.6] and 1.2 [95% confidence interval, 1.0–1.4], respectively). Patients with their third and fourth or more surgery in adulthood had a 2- and 3-times-higher risk of death compared with patients never operated on (adjusted hazard ratio=1.9 [95% confidence interval, 1.0–3.6] and 2.7 [95% confidence interval, 1.1–6.3], respectively). Men with a reoperation in adulthood had a 2-times-higher risk of death than women (adjusted hazard ratio=1.9; 95% confidence interval, 1.0–3.5).

Conclusions—
Of predominantly young adults with congenital heart disease, one fifth required cardiovascular surgery during a 15-year period; in 40%, the surgery was a reoperation. Men with congenital heart disease have a higher chance of undergoing surgery in adulthood and have a consistently worse long-term survival after reoperations in adulthood compared with women.
Effects of a Novel Aldosterone Synthase Inhibitor for Treatment of Primary Hypertension
Authors: Calhoun David A. , White William B. , Krum Henry , Guo Weinong , Bermann Georgina , Trapani Angelo , Lefkowitz Martin P. , Ménard Joël 
Published: October 2011

Background—
LCI699, a novel inhibitor of aldosterone synthase, reduces serum aldosterone, and may have benefit in the treatment of hypertension.

Methods and Results—

We performed the first double-blind, randomized trial with LCI699 in patients with primary hypertension. We randomized 524 patients to LCI699 0.25 mg once daily (n=92), 0.5 mg once daily (n=88), 1.0 mg once daily (n=86), and 0.5 mg twice daily (n=97); eplerenone 50 mg twice daily (n=84); or placebo (n=77) for 8 weeks. Adrenocorticotropic hormone (250 μg IV) stimulation testing was performed in a subset of patients to quantify the selectivity of LCI699 for aldosterone synthase compared with 11-β-hydroxylase. Reductions in clinic diastolic blood pressure were significant for LCI699 1.0 mg (−7.1 mm Hg;
P
=0.0012) and eplerenone 50 mg twice daily (−7.9 mm Hg;
P
<0.0001) compared with placebo (−2.6 mm Hg) but not other doses of LCI699. Significant reductions in clinic systolic blood pressure were observed with all doses of LCI699 (
P
<0.005 or better) and eplerenone (
P
<0.0001). All doses of LCI699 significantly reduced 24-hour ambulatory blood pressure compared with placebo (
P
<0.01). Adrenocorticotropic hormone stimulation of cortisol was suppressed in ≈20% of subjects receiving LCI699 at a total daily dose of 1.0 mg. Safety and tolerability were similar among LCI699, placebo, and eplerenone.

Conclusions—
Aldosterone synthase inhibition with LCI699 significantly lowered clinic and ambulatory blood pressure. A minority of subjects developed blunted adrenocorticotropic hormone–stimulated release of cortisol. These results support additional research to evaluate use of aldosterone synthase inhibition in primary hypertension and/or patients characterized by aldosterone excess.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00758524.
Intravital Microscopy on Atherosclerosis in Apolipoprotein E–Deficient Mice Establishes Microvessels as Major Entry Pathways for Leukocytes to Advanced Lesions
Authors: Eriksson Einar E. 
Published: October 2011

Background—
There has been considerable speculation about the role of lesion microvessels in the accumulation of leukocytes in atherosclerosis. However, direct study of microvascular recruitment of leukocytes in lesions has not been performed, and the quantitative role for this route of entry is unclear.

Methods and Results—

Here, microvascular recruitment of leukocytes was studied in advanced lesions in 12- to 24-month-old apolipoprotein E–deficient (ApoE
−/−
) mice. Histology and transmission electron microscopy demonstrated the presence of mainly adventitial, but also intimal, microvessels. Interactions between leukocytes and endothelium occurred in lesion venules. Leukocyte rolling was largely P-selectin dependent; however, residual rolling was mediated by L-selectin and endothelial P-selectin glycoprotein ligand 1. Leukocyte adhesion was significant and was attenuated in mice treated with antibodies against P-selectin, CD18, or both before preparation for intravital microscopy, suggesting acute activation of these 2 molecules by surgical trauma. Nonetheless, the density of firmly arrested leukocytes was 100-fold higher in lesion venules compared with the arterial lumen even in mice pretreated with antibodies against P-selectin and CD18, indicating strong recruitment of cells from venules that is unrelated to experimental manipulation. Fluorescent myelomonocytic cells in ApoE
−/−
mice carrying a knock-in mutation for enhanced green fluorescent protein (EGFP) in the lysozyme M locus (ApoE
−/−
/lysM
EGFP/EGFP
mice) were distributed specifically around lesion venules, but not around arterioles or capillaries, further indicating ongoing extravasation from venules into plaque tissue.

Conclusions—
These findings provide strong data for microvascular recruitment of leukocytes in atherosclerosis and indicate roles for L-selectin and P-selectin glycoprotein ligand 1 in this process.
Isolated Atrioventricular Block in the Fetus
Authors: Eliasson Håkan , Sonesson Sven-Erik , Sharland Gurleen , Granath Fredrik , Simpson John M. , Carvalho Julene S. , Jicinska Hana , Tomek Viktor , Dangel Joanna , Zielinsky Paulo , Respondek-Liberska Maria , Freund Matthias W. , Mellander Mats , Bartrons Joaquim , Gardiner Helena M. ,   for the Fetal Working Group of the European Association of Pediatric Cardiology
Published: October 2011

Background—
Isolated complete atrioventricular block in the fetus is a rare but potentially lethal condition in which the effect of steroid treatment on outcome is unclear. The objective of this work was to study risk factors associated with death and the influence of steroid treatment on outcome.

Methods and Results—

We studied 175 fetuses diagnosed with second- or third-degree atrioventricular block (2000–2007) retrospectively in a multinational, multicenter setting. In 80% of 162 pregnancies with documented antibody status, atrioventricular block was associated with maternal anti-Ro/SSA antibodies. Sixty-seven cases (38%) were treated with fluorinated corticosteroids for a median of 10 weeks (1–21 weeks). Ninety-one percent were alive at birth, and survival in the neonatal period was 93%, similar in steroid-treated and untreated fetuses, regardless of degree of block and/or presence of anti-Ro/SSA. Variables associated with death were gestational age <20 weeks, ventricular rate ≤50 bpm, fetal hydrops, and impaired left ventricular function at diagnosis. The presence of ≥1 of these variables was associated with a 10-fold increase in mortality before birth and a 6-fold increase in the neonatal period independently of treatment. Except for a lower gestational age at diagnosis in treated than untreated (23.4±2.9 versus 24.9±4.9 weeks;
P
=0.02), risk factors were distributed equally between treatment groups. Two-thirds of survivors had a pacemaker by 1 year of age; 8 children developed cardiomyopathy.

Conclusions—
Risk factors associated with a poor outcome were gestation <20 weeks, ventricular rate ≤50 bpm, hydrops, and impaired left ventricular function. No significant effect of treatment with fluorinated corticosteroids was seen.
Response of Upper Clouds in Global Warming Experiments Obtained Using a Global Nonhydrostatic Model with Explicit Cloud Processes
Authors: Satoh Masaki , Iga Shin-ichi , Tomita Hirofumi , Tsushima Yoko , Noda Akira T. 
Published: October 2011

AbstractUsing a global nonhydrostatic model with explicit cloud processes, upper-cloud changes are investigated by comparing the present climate condition under the perpetual July setting and the global warming condition, in which the sea surface temperature (SST) is raised by 2°. The sensitivity of the upper-cloud cover and the ice water path (IWP) are investigated through a set of experiments. The responses of convective mass flux and convective areas are also examined, together with those of the large-scale subsidence and relative humidity in the subtropics. The responses of the IWP and the upper-cloud cover are found to be opposite; that is, as the SST increases, the IWP averaged over the tropics decreases, whereas the upper-cloud cover in the tropics increases. To clarify the IWP response, a simple conceptual model is constructed. The model consists of three columns of deep convective core, anvil, and environmental subsidence regions. The vertical profiles of hydrometers are predicted with cloud microphysics processes and kinematically prescribed circulation. The reduction in convective mass flux is found to be a primary factor in the decrease of the IWP under the global warming condition. Even when a different and more comprehensive cloud microphysics scheme is used, the reduction in the IWP due to the mass flux change is also confirmed.
Monsoon Regimes and Processes in CCSM4. Part I: The Asian–Australian Monsoon
Authors: Meehl Gerald A. , Arblaster Julie M. , Caron Julie M. , Annamalai H. , Jochum Markus , Chakraborty Arindam , Murtugudde Raghu 
Published: October 2011

Abstract
The simulation characteristics of the Asian–Australian monsoon are documented for the Community Climate System Model, version 4 (CCSM4). This is the first part of a two part series examining monsoon regimes in the global tropics in the CCSM4. Comparisons are made to an Atmospheric Model Intercomparison Project (AMIP) simulation of the atmospheric component in CCSM4 [Community Atmosphere Model, version 4, (CAM4)] to deduce differences in the monsoon simulations run with observed sea surface temperatures (SSTs) and with ocean–atmosphere coupling. These simulations are also compared to a previous version of the model (CCSM3) to evaluate progress. In general, monsoon rainfall is too heavy in the uncoupled AMIP run with CAM4, and monsoon rainfall amounts are generally better simulated with ocean coupling in CCSM4. Most aspects of the Asian–Australian monsoon simulations are improved in CCSM4 compared to CCSM3. There is a reduction of the systematic error of rainfall over the tropical Indian Ocean for the South Asian monsoon, and well-simulated connections between SSTs in the Bay of Bengal and regional South Asian monsoon precipitation. The pattern of rainfall in the Australian monsoon is closer to observations in part because of contributions from the improvements of the Indonesian Throughflow and diapycnal diffusion in CCSM4. Intraseasonal variability of the Asian–Australian monsoon is much improved in CCSM4 compared to CCSM3 both in terms of eastward and northward propagation characteristics, though it is still somewhat weaker than observed. An improved simulation of El Niño in CCSM4 contributes to more realistic connections between the Asian–Australian monsoon and El Niño–Southern Oscillation (ENSO), though there is considerable decadal and century time scale variability of the strength of the monsoon–ENSO connection.
Shortwave Direction and Spreading Measured with HF Radar
Authors: Wyatt Lucy R. 
Published: October 2011

Abstract
The accuracy of wave direction and spreading at the Bragg-matched wavelength measured with HF radar over a wide range of HF operating frequencies is demonstrated by comparison with buoy data. The agreement for shortwave direction is better than that obtained for wind direction, which has been the more common application of this measurement, because these waves are not always aligned with the wind direction, particularly in short fetch and low wind speed situations. The method assumes a model of shortwave directionality and the validity of this is explored by using the buoy Fourier coefficients, with inconclusive results. The radar measurements do not use the linear dispersion relationship, but the comparison with buoy data does, and the implications of this are discussed.
Evolution and Maintenance of the 22–23 June 2003 Nocturnal Convection during BAMEX
Authors: Billings Jerilyn M. , Parker Matthew D. 
Published: October 2011

Abstract
On 22–23 June 2003 a broad region of convection, comprising a squall line and discrete supercells, evolved throughout the evening and nighttime hours. These storms were studied by analyzing both observations and idealized numerical simulations. The squall line originated from a group of supercells that were initiated in a north–south line along a preexisting outflow boundary in eastern Nebraska. These supercells anchored to the boundary, facilitating cell mergers. The cell mergers and subsequent enhanced rainfall increased the depth and strength of the surface cold pool, which became the forcing mechanism for reorientation into an east–west, southward-propagating squall line. While this was occurring, isolated supercells developed along the dryline in north-central Kansas. These supercells moved northeastward throughout the night. These two modes of convection developed and evolved in a similar nocturnal environment, suggesting that there were two distinct forcing mechanisms responsible for their maintenance. The nocturnal boundary layer was stable; however, CAPE existed and convection would have been able to remain surface based so long as near-surface air was being lifted to its level of free convection (LFC). In this study, both cold pool dynamics and supercell dynamics appear to have played an important roll in lifting low-level air to its LFC throughout the night.