bluuebunny/crossref_metadata_2025_split huggingface dataset:
G Protein–Coupled Receptor Kinase 2 Activity Impairs Cardiac Glucose Uptake and Promotes Insulin Resistance After Myocardial Ischemia
Authors: Ciccarelli Michele , Chuprun J. Kurt , Rengo Giuseppe , Gao Erhe , Wei Zhengyu , Peroutka Raymond J. , Gold Jessica I. , Gumpert Anna , Chen Mai , Otis Nicholas J. , Dorn Gerald W. , Trimarco Bruno , Iaccarino Guido , Koch Walter J. 
Published: April 2011

Background—
Alterations in cardiac energy metabolism downstream of neurohormonal stimulation play a crucial role in the pathogenesis of heart failure. The chronic adrenergic stimulation that accompanies heart failure is a signaling abnormality that leads to the upregulation of G protein–coupled receptor kinase 2 (GRK2), which is pathological in the myocyte during disease progression in part owing to uncoupling of the β-adrenergic receptor system. In this study, we explored the possibility that enhanced GRK2 expression and activity, as seen during heart failure, can negatively affect cardiac metabolism as part of its pathogenic profile.

Methods and Results—
Positron emission tomography studies revealed in transgenic mice that cardiac-specific overexpression of GRK2 negatively affected cardiac metabolism by inhibiting glucose uptake and desensitization of insulin signaling, which increases after ischemic injury and precedes heart failure development. Mechanistically, GRK2 interacts with and directly phosphorylates insulin receptor substrate-1 in cardiomyocytes, causing insulin-dependent negative signaling feedback, including inhibition of membrane translocation of the glucose transporter GLUT4. This identifies insulin receptor substrate-1 as a novel nonreceptor target for GRK2 and represents a new pathological mechanism for this kinase in the failing heart. Importantly, inhibition of GRK2 activity prevents postischemic defects in myocardial insulin signaling and improves cardiac metabolism via normalized glucose uptake, which appears to participate in GRK2-targeted prevention of heart failure.

Conclusions—
Our data provide novel insights into how GRK2 is pathological in the injured heart. Moreover, it appears to be a critical mechanistic link within neurohormonal crosstalk governing cardiac contractile signaling/function through β-adrenergic receptors and metabolism through the insulin receptor.
Preoperative Factors Associated With Adverse Outcome After Tricuspid Valve Replacement
Authors: Topilsky Yan , Khanna Amber D. , Oh Jae K. , Nishimura Rick A. , Enriquez-Sarano Maurice , Jeon Yang B. , Sundt Thoralf M. , Schaff Hartzell V. , Park Soon J. 
Published: April 2011

Background—
Preoperative factors associated with increased mortality and worse outcome after tricuspid valve replacement in patients with severe tricuspid regurgitation are poorly understood.

Methods and Results—

We retrospectively analyzed 189 patients (37% men; age, 67.5±11.3 years) who underwent tricuspid valve replacement for severe tricuspid regurgitation. Operative mortality rate was 10%, and was associated with intra-aortic balloon pump (odds ratio, 3.2; 95% confidence interval, 1.9 to 5.6;
P
<0.0001) or the presence of severe symptoms (New York Heart Association class IV relative to classes II and/or III) at the time of surgery (1.7; 95% confidence interval, 1.05 to 2.8;
P
=0.02). At the end of follow-up (29.3±27.1 months), 70 patients (37%) died, 6 (3%) needed tricuspid reoperation, and 41 (21.7%) were readmitted for heart failure. Seventy-eight patients (41.3%) were free from cardiovascular events (death, tricuspid reoperation, or heart failure admissions). The only echocardiographic parameter independently associated with adverse outcomes was a decrease in the right index of myocardial performance ratio. All-cause mortality was independently associated with a higher Charlson index (hazard ratio, 1.18; 95% confidence interval, 1.01 to 1.36;
P
=0.03), shorter right index of myocardial performance ratio (0.91; 95% confidence interval, 0.87 to 0.96;
P
=0.005), and preoperative New York Heart Association IV class (1.71; 95% confidence interval, 1.3 to 2.2;
P
<0.0001). In 68 patients with isolated tricuspid valve replacement, the associations between short right index of myocardial performance ratio, high Charlson index, New York Heart Association class IV, and increased mortality remained significant.

Conclusions—
Tricuspid valve replacement for severe tricuspid regurgitation can be performed with an acceptable operative mortality if patients undergo surgery before the onset of advanced heart failure symptoms. Late mortality is associated with a high preoperative Charlson index, short right index of myocardial performance ratio, and advanced New York Heart Association class.
Effect of Renal Sympathetic Denervation on Glucose Metabolism in Patients With Resistant Hypertension
Authors: Mahfoud Felix , Schlaich Markus , Kindermann Ingrid , Ukena Christian , Cremers Bodo , Brandt Mathias C. , Hoppe Uta C. , Vonend Oliver , Rump Lars C. , Sobotka Paul A. , Krum Henry , Esler Murray , Böhm Michael 
Published: April 2011

Background—
Hypertension is associated with impaired glucose metabolism and insulin resistance. Chronic activation of the sympathetic nervous system may contribute to either condition. We investigated the effect of catheter-based renal sympathetic denervation on glucose metabolism and blood pressure control in patients with resistant hypertension.

Methods and Results—

We enrolled 50 patients with therapy-resistant hypertension. Thirty-seven patients underwent bilateral catheter-based renal denervation, and 13 patients were assigned to a control group. Systolic and diastolic blood pressures, fasting glucose, insulin, C peptide, hemoglobin A
1c
, calculated insulin sensitivity (homeostasis model assessment–insulin resistance), and glucose levels during oral glucose tolerance test were measured before and 1 and 3 months after treatment. Mean office blood pressure at baseline was 178/96±3/2 mm Hg. At 1 and 3 months, office blood pressure was reduced by −28/−10 mm Hg (
P
<0.001) and −32/−12 mm Hg (
P
<0.001), respectively, in the treatment group, without changes in concurrent antihypertensive treatment. Three months after renal denervation, fasting glucose was reduced from 118±3.4 to 108±3.8 mg/dL (
P
=0.039). Insulin levels were decreased from 20.8±3.0 to 9.3±2.5 μIU/mL (
P
=0.006) and C-peptide levels from 5.3±0.6 to 3.0±0.9 ng/mL (
P
=0.002). After 3 months, homeostasis model assessment–insulin resistance decreased from 6.0±0.9 to 2.4±0.8 (
P
=0.001). Additionally, mean 2-hour glucose levels during oral glucose tolerance test were reduced significantly by 27 mg/dL (
P
=0.012). There were no significant changes in blood pressure or metabolic markers in the control group.

Conclusions—
Renal denervation improves glucose metabolism and insulin sensitivity in addition to a significantly reducing blood pressure. However, this improvement appeared to be unrelated to changes in drug treatment. This novel procedure may therefore provide protection in patients with resistant hypertension and metabolic disorders at high cardiovascular risk.

Clinical Trial Registration—

URL:
http://www.ClinicalTrials.gov
. Unique identifiers: NCT00664638 and NCT00888433.
Visual and Auditory Augmented Concurrent Feedback in a Complex Motor Task
Authors: Sigrist Roland 
Published: April 2011

In general, concurrent augmented feedback has been shown to effectively enhance learning in complex motor tasks. However, to optimize technical systems that are intended to reinforce motor learning, a systematic evaluation of different augmented feedback designs is required. Until now, mainly visual augmented feedback has been applied to enhance learning of complex motor tasks. Since most complex motor tasks are mastered in response to information visually perceived, providing augmented concurrent feedback in a visual manner may overload the capacities of visual perception and cognitive processing. Thus, the aim of this work was to evaluate the practicability of auditory feedback designs supporting a three-dimensional rowing-type movement in comparison with visual feedback designs. We term a feedback design practical if the provided information can easily be perceived and interpreted, and immediately be used to support the movement. In a first experiment, it became evident that participants could interpret three-dimensional auditory feedback designs based on stereo balance, pitch, timbre, and/or volume. Eleven of 12 participants were able to follow the different target movements using auditory feedback designs as accurately as with a very abstract visual feedback design. Visual designs based on superposition of actual and target oar orientation led to the most accurate performance. Considering the first experimental results, the feedback designs were further developed and again evaluated. It became evident that a permanent visual display of the target trajectories could further enhance movement accuracy. Moreover, results indicated that the practicability of the auditory designs depends on the polarity of the mapping functions. In general, both visual and auditory concurrent feedback designs were practical to immediately support multidimensional movement. In a next step, the effectiveness to enhance motor learning will be systematically evaluated.
Seasonal Modes of Surface Cooling in the Gulf of Guinea
Authors: Jouanno Julien , Marin Frédéric , du Penhoat Yves , Molines Jean Marc , Sheinbaum Julio 
Published: April 2011

Abstract
A numerical simulation of the tropical Atlantic Ocean indicates that surface cooling in upwelling zones of the Gulf of Guinea is mostly due to vertical mixing. At the seasonal scale, the spatial structure and the time variability of the northern and southern branches of the South Equatorial Current (SEC), and of the Guinea Current, are correlated with the timing and distribution of turbulent heat fluxes in the Gulf of Guinea. Through modulation of the velocity shear at the subsurface, these surface currents control the vertical turbulent exchanges, bringing cold and nutrient-rich waters to the surface. This mechanism explains the seasonality and spatial distribution of surface chlorophyll concentrations better than the generally accepted hypothesis that thermocline movements control the nutrient flux. The position of the southern SEC explains why the cold tongue and high chlorophyll concentrations extend from the equator to 4°S in the southeastern part of the basin.
Development and Application of a Compact, Tunable, Solid-State Airborne Ozone Lidar System for Boundary Layer Profiling
Authors: Alvarez R. J. , Senff C. J. , Langford A. O. , Weickmann A. M. , Law D. C. , Machol J. L. , Merritt D. A. , Marchbanks R. D. , Sandberg S. P. , Brewer W. A. , Hardesty R. M. , Banta R. M. 
Published: April 2011

Abstract
The National Oceanic and Atmospheric Administration/Earth System Research Laboratory/Chemical Sciences Division (NOAA/ESRL/CSD) has developed a versatile, airborne lidar system for measuring ozone and aerosols in the boundary layer and lower free troposphere. The Tunable Optical Profiler for Aerosol and Ozone (TOPAZ) lidar was deployed aboard a NOAA Twin Otter aircraft during the Texas Air Quality Study (TexAQS 2006) and the California Research at the Nexus of Air Quality and Climate Change (CalNex 2010) field campaigns. TOPAZ is capable of measuring ozone concentrations in the lower troposphere with uncertainties of several parts per billion by volume at 90-m vertical and 600-m horizontal resolution from an aircraft flying at 60 m s−1. The system also provides uncalibrated aerosol backscatter profiles at 18-m vertical and 600-m horizontal resolution. TOPAZ incorporates state-of-the-art technologies, including a cerium-doped lithium calcium aluminum fluoride (Ce:LiCAF) laser, to make it compact and lightweight with low power consumption. The tunable, three-wavelength UV laser source makes it possible to optimize the wavelengths for differing atmospheric conditions, reduce the interference from other atmospheric constituents, and implement advanced analysis techniques. This paper describes the TOPAZ lidar, its components and performance during testing and field operation, and the data analysis procedure, including a discussion of error sources. The performance characteristics are illustrated through a comparison between TOPAZ and an ozonesonde launched during the TexAQS 2006 field campaign. A more comprehensive set of comparisons with in situ measurements during TexAQS 2006 and an assessment of the TOPAZ accuracy and precision are presented in a companion paper.
Temporal–Spatial Distribution of Atmospheric Predictability Limit by Local Dynamical Analogs
Authors: Li Jianping , Ding Ruiqiang 
Published: April 2011

AbstractTo quantify the predictability limit of a chaotic system, the authors recently developed a method using the nonlinear local Lyapunov exponent (NLLE). The NLLE method provides a measure of local predictability limit of chaotic systems and is intended to supplement existing predictability methods. To apply the NLLE in studies of actual atmospheric predictability, an algorithm based on local dynamical analogs is devised to enable the estimation of the NLLE and its derivatives using experimental or observational data. Two examples are given to illustrate the effectiveness of the algorithm, involving the Lorenz63 three-variable model and the Lorenz96 forty-variable model; they reveal that the algorithm is applicable in estimating the NLLE of a chaotic system from its experimental time series. On this basis, the NLLE method is used to investigate temporal–spatial distributions of predictability limits of the daily geopotential height and wind fields. The limit of atmospheric predictability varies widely with region, altitude, and season. The predictability limits of the daily geopotential height and wind fields are generally less than 3 weeks in the troposphere, whereas they are approximately 1 month in the lower stratosphere, revealing a potential predictability source for forecasting weather from the stratosphere. Further work is required to examine broader applications of the NLLE method in predictability studies of the atmosphere, ocean, and other systems.
RUNX1 regulates corepressor interactions of PU.1
Authors: Hu Zhenbo , Gu Xiaorong , Baraoidan Kristine , Ibanez Vinzon , Sharma Arun , Kadkol ShriHari , Munker Reinhold , Ackerman Steven , Nucifora Giuseppina , Saunthararajah Yogen 
Published: April 2011

Abstract
The transcription factor (TF) RUNX1 cooperates with lineage-specifying TFs (eg, PU.1/SPI1) to activate myeloid differentiation genes, such as macrophage and granulocyte macrophage colony-stimulating factor receptors (MCSFR and GMCSFR). Disruption of cooperative gene activation could contribute to aberrant repression of differentiation genes and leukemogenesis initiated by mutations and translocations of RUNX1. To investigate the mechanisms underlying cooperative gene activation, the effects of Runx1 deficiency were examined in an in vitro model of Pu.1-driven macrophage differentiation and in primary cells. Runx1 deficiency decreased Pu.1-mediated activation of Mcsfr and Gmcsfr, accompanied by decreased histone acetylation at the Mcsfr and Gmcsfr promoters, and increased endogenous corepressor (Eto2, Sin3A, and Hdac2) coimmunoprecipitation with Pu.1. In cotransfection experiments, corepressors were excluded from a multiprotein complex containing full-length RUNX1 and PU.1. However, corepressors interacted with PU.1 if wild-type RUNX1 was replaced with truncated variants associated with leukemia. Histone deacetylase (HDAC) enzyme activity is a major component of corepressor function. HDAC inhibition using suberoylanilide hydroxamic acid or MS-275 significantly increased MCSFR and GMCSFR expression in leukemia cell lines that express PU.1 and mutated or translocated RUNX1. RUNX1 deficiency is associated with persistent corepressor interaction with PU.1. Thus, inhibiting HDAC can partly compensate for the functional consequences of RUNX1 deficiency.
Recombinant interferon-α may retard progression of early primary myelofibrosis: a preliminary report
Authors: Silver Richard T. , Vandris Katherine , Goldman Joshua J. 
Published: April 2011

Abstract
The limited effects of current treatments of primary myelofibrosis (PM) led us to prospectively evaluate recombinant interferon-α (rIFNα) in “early” PM patients with residual hematopoiesis and only grade 1 or 2 myelofibrosis. Seventeen patients meeting World Health Organization PM diagnostic criteria received either rIFNα-2b 500 000 to 3 million units 3 times weekly, or pegylated rIFNα-2a 45 or 90 μg weekly. International Working Group for Myelofibrosis Research and Treatment criteria for prognosis and response were used. Eleven patients were women and 6 were men. Their median age at diagnosis was 57 years. Eleven patients were low risk and 6 were intermediate-1 risk. Two achieved complete remission, 7 partial, 1 clinical improvement, 4 stable disease, and 3 had progressive disease. Thus, more than 80% derived clinical benefit or stability. Improvement in marrow morphology occurred in 4. Toxicity was acceptable. These results, with documented marrow reversion because of interferon treatment, warrant expanded evaluation.
MLL fusion proteins preferentially regulate a subset of wild-type MLL target genes in the leukemic genome
Authors: Wang Qian-fei , Wu George , Mi Shuangli , He Fuhong , Wu Jun , Dong Jingfang , Luo Roger T. , Mattison Ryan , Kaberlein Joseph J. , Prabhakar Shyam , Ji Hongkai , Thirman Michael J. 
Published: April 2011

Abstract
MLL encodes a histone methyltransferase that is critical in maintaining gene expression during embryonic development and hematopoiesis. 11q23 translocations result in the formation of chimeric MLL fusion proteins that act as potent drivers of acute leukemia. However, it remains unclear what portion of the leukemic genome is under the direct control of MLL fusions. By comparing patient-derived leukemic cell lines, we find that MLL fusion-bound genes are a small subset of that recognized by wild-type MLL. In an inducible MLL-ENL model, MLL fusion protein binding and changes in H3K79 methylation are limited to a specific portion of the genome, whereas wild-type MLL distributes to a much larger set of gene loci. Surprisingly, among 223 MLL-ENL–bound genes, only 12 demonstrate a significant increase in mRNA expression on induction of the fusion protein. In addition to Hoxa9 and Meis1, this includes Eya1 and Six1, which comprise a heterodimeric transcription factor important in several developmental pathways. We show that Eya1 has the capacity to immortalize hematopoietic progenitor cells in vitro and collaborates with Six1 in hematopoietic transformation assays. Altogether, our data suggest that MLL fusions contribute to the development of acute leukemia through direct activation of a small set of target genes.
SUVmax reduction improves early prognosis value of interim positron emission tomography scans in diffuse large B-cell lymphoma
Authors: Casasnovas René-Olivier , Meignan Michel , Berriolo-Riedinger Alina , Bardet Stéphane , Julian Anne , Thieblemont Catherine , Vera Pierre , Bologna Serge , Brière Josette , Jais Jean-Philippe , Haioun Corinne , Coiffier Bertrand , Morschhauser Franck 
Published: April 2011

AbstractThe prognostic value of interim positron emission tomography (PET) interpreted according to visual criteria is a matter of debate in diffuse large B-cell lymphoma (DLBCL). Maximal standardized uptake value reduction (ΔSUVmax) may better predict outcome. To compare the prognostic value of both methods, we analyzed PET done at baseline (PET0) and after 2 (PET2) and 4 (PET4) cycles in 85 patients with high-risk DLBCL enrolled on a prospective multicenter trial. All images were centrally reviewed and interpreted visually according to the International Harmonization Project criteria and by computing ΔSUVmax between PET0 and PET2 (ΔSUVmaxPET0-2) or PET4 (ΔSUVmaxPET0-4). Optimal cutoff to predict progression or death was 66% for ΔSUVmaxPET0-2 and 70% for ΔSUVmaxPET0-4. Outcomes did not differ significantly whether PET2 and PET4 were visually positive or negative. Inversely, ΔSUVmaxPET0-2 analysis (> 66% vs ≤ 66%) identified patients with significantly different 2-year progression-free survival (77% vs 57%; P = .0282) and overall survival (93% vs 60%; P < .0001). ΔSUVmaxPET0-4 analysis (> 70% vs ≤ 70%) seemed even more predictive for 2-year progression-free survival (83 vs 40%; P < .0001) and overall survival (94% vs 50%; P < .0001). ΔSUVmax analysis of sequential interim PET is feasible for high-risk DLBCL and better predicts outcome than visual analysis. The trial was registered at http://clinicaltrials.gov as NCT00498043.
NKG2D receptor regulates human effector T-cell cytokine production
Authors: Barber Amorette , Sentman Charles L. 
Published: April 2011

AbstractAlthough innate immune signals shape the activation of naive T cells, it is unclear how innate signals influence effector T-cell function. This study determined the effects of stimulating the NKG2D receptor in conjunction with the TCR on human effector CD8+ T cells. Stimulation of CD8+ T cells through CD3 and NKG2D simultaneously or through a chimeric NKG2D receptor, which consists of NKG2D fused to the intracellular region of CD3ζ, activated β-catenin and increased expression of β-catenin–induced genes, whereas T cells stimulated through the TCR or a combination of the TCR and CD28 did not. Activation by TCR and NKG2D prevented expression and production of anti-inflammatory cytokines IL-10, IL-9, IL-13, and VEGF-α in a β-catenin– and PPARγ- dependent manner. NKG2D stimulation also modulated the cytokine secretion of T cells activated simultaneously through CD3 and CD28. These data indicate that activating CD8+ T cells through the NKG2D receptor along with the TCR modulates signal transduction and the production of anti-inflammatory cytokines. Thus, human effector T cells alter their function depending on which innate receptors are engaged in conjunction with the TCR complex.
Pulmonary arterial dysfunction in insulin resistant obese Zucker rats
Authors: Moral-Sanz Javier , Menendez Carmen , Moreno Laura , Moreno Enrique , Cogolludo Angel , Perez-Vizcaino Francisco 
Published: April 2011

Abstract

Background
Insulin resistance and obesity are strongly associated with systemic cardiovascular diseases. Recent reports have also suggested a link between insulin resistance with pulmonary arterial hypertension. The aim of this study was to analyze pulmonary vascular function in the insulin resistant obese Zucker rat.

Methods
Large and small pulmonary arteries from obese Zucker rat and their lean counterparts were mounted for isometric tension recording. mRNA and protein expression was measured by RT-PCR or Western blot, respectively. KV currents were recorded in isolated pulmonary artery smooth muscle cells using the patch clamp technique.

Results
Right ventricular wall thickness was similar in obese and lean Zucker rats. Lung BMPR2, KV1.5 and 5-HT2A receptor mRNA and protein expression and KV current density were also similar in the two rat strains. In conductance and resistance pulmonary arteries, the similar relaxant responses to acetylcholine and nitroprusside and unchanged lung eNOS expression revealed a preserved endothelial function. However, in resistance (but not in conductance) pulmonary arteries from obese rats a reduced response to several vasoconstrictor agents (hypoxia, phenylephrine and 5-HT) was observed. The hyporesponsiveness to vasoconstrictors was reversed by L-NAME and prevented by the iNOS inhibitor 1400W.

Conclusions
In contrast to rat models of type 1 diabetes or other mice models of insulin resistance, the obese Zucker rats did not show any of the characteristic features of pulmonary hypertension but rather a reduced vasoconstrictor response which could be prevented by inhibition of iNOS.