bluuebunny/crossref_metadata_2025_split huggingface dataset:
Renalase Lowers Ambulatory Blood Pressure by Metabolizing Circulating Adrenaline
Authors: Desir Gary V. , Tang LieQi , Wang Peili , Li Guoyong , Sampaio‐Maia Benedita , Quelhas‐Santos Janete , Pestana Manuel , Velazquez Heino 
Published: September 2012

Background
Blood pressure is acutely regulated by the sympathetic nervous system through the action of vasoactive hormones such as epinephrine, norepinephrine, and dopamine. Renalase, a recently described, secreted flavoprotein, acutely decreases systemic pressure when administered in vivo. Single‐nucleotide polymorphisms present in the gene are associated with hypertension, cardiac disease, and diabetes. Although renalase's crystal structure was recently solved, its natural substrate(s) remains undefined.

Methods and Results
Using in vitro enzymatic assays and in vivo administration of recombinant renalase, we show that the protein functions as a flavin adenine dinucleotide– and nicotinamide adenine dinucleotide–dependent oxidase that lowers blood pressure by degrading plasma epinephrine. The enzyme also metabolizes the dopamine precursor L‐3,4‐dihydroxyphenylalanine but has low activity against dopamine and does not metabolize norepinephrine. To test if epinephrine and L‐3,4‐dihydroxyphenylalanine were renalase's only substrates, 17 246 unique small molecules were screened. Although the search revealed no additional, naturally occurring compounds, it identified dobutamine, isoproterenol, and α‐methyldopa as substrates of renalase. Mutational analysis was used to test if renalase's hypotensive effect correlated with its enzymatic activity. Single–amino acid mutations that decrease its enzymatic activity to varying degrees comparably reduce its hypotensive effect.

Conclusions

Renalase metabolizes circulating epinephrine and L‐3,4‐dihydroxyphenylalanine, and its capacity to decrease blood pressure is directly correlated to its enzymatic activity. These findings highlight a previously unrecognized mechanism for epinephrine metabolism and blood pressure regulation, expand our understanding of the sympathetic nervous system, and could lead to the development of novel therapeutic modalities for the treatment of hypertension. (
J Am Heart Assoc
. 2012;1:e002634 doi: 10.1161/
JAHA
.112.002634.)
Association Between Depression and Peripheral Artery Disease: Insights From the Heart and Soul Study
Authors: Grenon S. Marlene , Hiramoto Jade , Smolderen Kim G. , Vittinghoff Eric , Whooley Mary A. , Cohen Beth E. 
Published: September 2012

Background

Depression is known to increase the risk of coronary artery disease, but few studies have evaluated the association between depression and peripheral artery disease (
PAD
). We examined the association of depression with
PAD
and evaluated potential mediators of this association.

Methods and Results

We used data from the Heart and Soul Study, a prospective cohort of 1024 men and women with coronary artery disease recruited in 2000–2002 and followed for a mean of 7.2±2.6 years. Depressive symptoms were assessed with the validated 9‐item Patient Health Questionnaire. Prevalent PAD at baseline was determined by self‐report. Prospective PAD events were adjudicated on the basis of review of medical records. We used logistic regression and Cox proportional‐hazards models to estimate the independent associations of depressive symptoms with prevalent PAD and subsequent PAD events. At baseline, 199 patients (19%) had depressive symptoms (Patient Health Questionnaire ≥10). Prevalent PAD was reported by 12% of patients with depression and 7% of those without depression (base model adjusted for age and sex: odds ratio 1.79, 95% confidence interval 1.06–3.04,
P
=0.03; full model adjusted for comorbidities, medications, PAD risk factors, inflammation, and health behaviors: odds ratio 1.59, 95% confidence interval 0.90–2.83,
P
=0.11). During follow‐up, PAD events occurred in 7% of patients with depression and 5% of those without depression (base model adjusted for age and sex: hazard ratio 2.09, 95% confidence interval 1.09–4.00,
P
=0.03; full model adjusted for comorbidities, medications, PAD risk factors, inflammation, and health behaviors: hazard ratio 1.33, 95% confidence interval 0.65–2.71,
P
=0.44). Factors explaining >5% of the association between depression and incident PAD events included race/ethnicity, diabetes, congestive heart failure, high‐density lipoprotein, triglyceride levels, serum creatinine, inflammation, smoking, and levels of physical activity.

Conclusions
Depressive symptoms were associated with a greater risk of PAD. Because the association was explained partly by modifiable risk factors, our findings suggest that more aggressive treatment of these risk factors could reduce the excess risk of PAD associated with depression.
Treatment of Small Ruptured Intracranial Aneurysms: Comparison of Surgical and Endovascular Options
Authors: Chalouhi Nohra , Penn David L. , Tjoumakaris Stavropoula , Jabbour Pascal , Gonzalez L. Fernando , Starke Robert M. , Ali Muhammad S. , Rosenwasser Robert , Dumont Aaron S. 
Published: September 2012

Background
Small intracranial aneurysms pose significant challenges to endovascular therapy. Surgical clipping is considered by many to be the preferred treatment for these lesions. We present the results of the first study comparing the 2 treatment modalities in small ruptured aneurysms.

Methods and Results

Between 2004 and 2011, 151 patients with small ruptured aneurysms (≤3 mm) were treated in our institution: 91 (60.3%) with endovascular therapy and 60 (39.7%) with surgical clipping. The surgical and endovascular groups were generally comparable with regard to baseline demographics, with the exception of larger mean aneurysm size in the endovascular group versus the surgical group (2.8 versus 2.5 mm, respectively;
P
<0.001) and a higher proportion of posterior circulation aneurysms in the endovascular group. Endovascular treatment failed in 9.9% of patients. Procedure‐related complications occurred in 23.3% of surgical patients versus 9.8% of endovascular patients (
P
=0.01). Only 3.7% of patients undergoing endovascular therapy experienced an intraprocedural aneurysm rupture. There were no procedural deaths or rehemorrhages in either group. The rates of aneurysm recanalization and retreatment after endovascular therapy were 18.2% and 12.7%, respectively. Favorable outcomes (moderate, mild, or no disability) were not statistically different between the endovascular (67.1%) and surgical (56.7%) groups (
P
=0.3).

Conclusions
Surgical clipping was associated with a higher rate of periprocedural complications, but overall disability outcomes were similar. Endovascular therapy, if technically feasible, might be a preferred option in this setting. Inclusion of patients with small aneurysms in randomized controlled trials seems feasible and will be needed to provide definitive information on the best therapeutic approach.
Novel Therapy for Atherosclerosis Using Recombinant Immunotoxin Against Folate Receptor β–Expressing Macrophages
Authors: Furusho Yuko , Miyata Masaaki , Matsuyama Takami , Nagai Taku , Li Hua , Akasaki Yuichi , Hamada Narisato , Miyauchi Takahiro , Ikeda Yoshiyuki , Shirasawa Takahiro , Ide Kanako , Tei Chuwa 
Published: September 2012

Background

Folate receptor β (
FR
β) is induced during macrophage activation. A recombinant immunotoxin consisting of the truncated

P
seudomonas

exotoxin A (
PE
38) conjugated to an anti‐
FR
β antibody (anti–
FR
β‐
PE
38) has been reported to kill activated macrophages in inflammatory diseases. To elucidate the effect of an immunotoxin targeting
FR
β on atherosclerosis, we determined the presence of
FR
β‐expressing macrophages in atherosclerotic lesions and administered the
FR
β immunotoxin in apolipoprotein E–deficient mice.

Methods and Results

The
FR
β‐expressing macrophages were observed in atherosclerotic lesions of apolipoprotein E–deficient mice. At 15 or 35 weeks of age, the apolipoprotein E–deficient mice were divided into 3 groups and were intravenously administered 0.1 mg/kg of anti–FRβ‐PE38 (immunotoxin group), 0.1 mg/kg of PE38 (toxin group), or 0.1 mL of saline (control group) every 3 days, for a total of 5 times for each age group. The mice were analyzed at 21 or 41 weeks of age. Treatment with the immunotoxin resulted in 31% and 22% reductions in atherosclerotic lesions of the 21‐ and 41‐week‐old mice, respectively (
P
<0.05). Administration of immunotoxin reduced the numbers of
FR
β‐ and tumor necrosis factor‐α–expressing macrophages, reduced cell proliferation, and increased the number of apoptotic cells (
P
<0.05). Real‐time polymerase chain reaction demonstrated that the expression of
FR
β and tumor necrosis factor‐α
mRNA
was significantly decreased in the immunotoxin group (
P
<0.05).

Conclusions

These results suggest that
FR
β‐expressing macrophages exist in the atherosclerotic lesions of apolipoprotein E–deficient mice and that
FR
β immunotoxin administration reduces the progression of atherosclerotic lesions in younger and older individuals. The recombinant
FR
β immunotoxin targeting activated macrophages could provide a novel therapeutic tool for atherosclerosis.
External Counterpulsation Augments Blood Pressure and Cerebral Flow Velocities in Ischemic Stroke Patients With Cerebral Intracranial Large Artery Occlusive Disease
Authors: Lin Wenhua , Xiong Li , Han Jinghao , Leung Thomas Wai Hong , Soo Yannie Oi Yan , Chen Xiangyan , Wong Ka Sing Lawrence 
Published: September 2012

Background and Purpose—
External counterpulsation (ECP) is a novel noninvasive method used to improve the perfusion of vital organs, which may benefit ischemic stroke patients. We hypothesized that ECP may augment cerebral blood flow of ischemic stroke patients via induced hypertension.

Methods—
We recruited ischemic stroke patients with cerebral intracranial large artery occlusive disease and healthy elderly controls into this study. Bilateral middle cerebral arteries of subjects were monitored using transcranial Doppler. Flow velocity changes before, during, and after ECP were, respectively, recorded for 3 minutes while continuous beat-to-beat blood pressure data were recorded. Cerebral augmentation index was the increase in percentage of middle cerebral artery mean flow velocity during ECP compared with baseline. Transcranial Doppler data were analyzed based on ipsilateral or contralateral to the infarct side.

Results—

ECP significantly increased mean blood pressure of stroke patients and controls. During ECP, middle cerebral artery mean flow velocities of stroke patients increased on both ipsilateral and contralateral sides when compared with baseline (ipsilateral cerebral augmentation index, 9.64%; contralateral cerebral augmentation index, 9%; both
P
<0.001), but there was no increase in difference between the 2 sides when compared with each other. Mean flow velocities of controls did not change under ECP. After ECP, blood pressure and flow velocity of stroke patients returned to baseline level.

Conclusion—
ECP provides a new method of cerebral blood flow augmentation in ischemic stroke by elevation of blood pressure. Flow augmentation induced by ECP suggests the improvement of cerebral perfusion and collateral supply from infarct ipsilateral and contralateral sides.
The Cerebral Autosomal-Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy (CADASIL) Scale
Authors: Pescini Francesca , Nannucci Serena , Bertaccini Bruno , Salvadori Emilia , Bianchi Silvia , Ragno Michele , Sarti Cristina , Valenti Raffaella , Zicari Enza , Moretti Marco , Chiti Stefano , Stromillo Maria Laura , De Stefano Nicola , Dotti Maria Teresa , Federico Antonio , Inzitari Domenico , Pantoni Leonardo 
Published: September 2012

Background and Purpose—
Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) phenotype is highly variable, and, although the full clinical–neuroimaging picture may be suggestive of the disease, no characteristic is pathognomonic. Thus, a genetic test remains the diagnostic gold standard, but because it is costly and time-consuming, a pregenetic screening appears desirable. We aimed at developing the CADASIL scale, a screening tool to be applied in the clinical setting.

Methods—

A preliminary scale was created assigning weighted scores to common disease features based on their frequencies obtained in a pooled analysis of selected international CADASIL series. The accuracy of the scale versus the genetic diagnosis was tested with receiver operating characteristic analysis after the application of this scale to 61 CADASIL and 54
NOTCH3
-negative patients (no pathogenic mutation on exons 2–23 of the
NOTCH3
gene). To improve the scale accuracy, we then developed an ad hoc optimization algorithm to detect the definitive scale. A third group of 39 patients affected by sporadic small-vessel disease was finally included in the algorithm to evaluate the stability of the scale.

Results—
The cutoff score of the definitive CADASIL scale had a sensitivity of 96.7% and a specificity of 74.2%. This scale was robust to contamination of patients with sporadic small-vessel disease.

Conclusions—
The CADASIL scale is a simple and sufficiently accurate screening tool to select patients with a high probability to be affected by the disease and therefore to be subjected to the genetic testing.
Immediate Hypothermia Is Not Neuroprotective After Severe Hypoxia-Ischemia and Is Deleterious When Delayed by 12 Hours in Neonatal Rats
Authors: Sabir Hemmen , Scull-Brown Emma , Liu Xun , Thoresen Marianne 
Published: September 2012

Background and Purpose—
Hypothermia (HT) for neonatal hypoxic-ischemic encephalopathy is advised to start within the first 6 hours after birth. There is some clinical evidence that HT is more effective against moderate than against severe hypoxic-ischemic encephalopathy, but it is unknown whether delayed HT beyond 6 hours is effective or even injurious.

Methods—
One-hundred seven 7-day-old rat pups underwent unilateral hypoxia-ischemia of moderate severity. Pups were randomized to receive 5 hours of normothermia (NT) or HT starting immediately, 3 hours, 6 hours, or 12 hours after the 90-minute hypoxic period. One-hundred five 7-day-old rat pups underwent severe hypoxia-ischemia lasting 150 minutes, followed by the same group design as mentioned. Relative area loss of the left/right hemisphere was measured after 1 week of survival.

Results—

In the moderate NT group, the mean area loss of the left hemisphere was 40.5%. The area loss was significantly decreased to 24.8% with immediate HT (
P
<0.05) and increased linearly with the delay of HT by 1.788% per hour until at least 6 hours of delay (linear regression,
P
=0.026). After 12-hour delayed HT, the area loss was similar to the moderate NT group (41.1%). After severe NT, the mean area loss of the left hemisphere was 59.3%. Immediate HT, 3-hour delayed HT, and 6-hour delayed HT all resulted in similar area loss, whereas the 12-hour delayed-HT resulted in significantly increased area loss (69.5%;
P
=0.032).

Conclusions—
Immediate and delayed (≤6 hours) HT provides neuroprotection after moderate hypoxia-ischemia in neonatal rats. This neuroprotection decreases linearly with increasing delay. After severe insults, however, immediate or delayed HT ≤6 hours provides no neuroprotection. Twelve-hour delayed hypothermia increased brain injury after severe hypoxia-ischemia, which is of clinical concern.
Exploring a Global Multiresolution Modeling Approach Using Aquaplanet Simulations*
Authors: Rauscher Sara A. , Ringler Todd D. , Skamarock William C. , Mirin Arthur A. 
Published: September 2012

Abstract
Results from aquaplanet experiments performed using the Model for Prediction across Scales (MPAS) hydrostatic dynamical core implemented within the Department of Energy (DOE)–NCAR Community Atmosphere Model (CAM) are presented. MPAS is an unstructured-grid approach to climate system modeling that supports both quasi-uniform and variable-resolution meshing of the sphere based on conforming grids. Using quasi-uniform simulations at resolutions of 30, 60, 120, and 240 km, the authors evaluate the performance of CAM-MPAS via its kinetic energy spectra, general circulation, and precipitation characteristics. By analyzing an additional variable-resolution simulation with grid spacing that varies from 30 km in a spherical, continental-sized equatorial region to 240 km elsewhere, the CAM-MPAS’s potential for use as a regional climate simulation tool is explored.
Similar to other quasi-uniform aquaplanet simulations, tropical precipitation increases with resolution, indicating the resolution sensitivity of the physical parameterizations. Comparison with the finite volume (FV) dynamical core suggests a weaker tropical circulation in the CAM-MPAS simulations, which is evident in reduced tropical precipitation and a weaker Hadley circulation. In the variable-resolution simulation, the kinetic energy spectrum within the high-resolution region closely resembles the quasi-uniform 30-km simulation, indicating a robust simulation of the fluid dynamics. As suggested by the quasi-uniform simulations, the CAM4 physics behave differently in the high and low resolution regions. A positive precipitation anomaly occurs on the western edge of the high-resolution region, exciting a Gill-type response; this zonal asymmetry represents the errors incurred in a variable resolution setting. When paired with a multiresolution mesh, the aquaplanet test case offers an exceptional opportunity to examine the response of physical parameterizations to grid resolution.
Diurnal Cycle in Different Weather Regimes and Rainfall Variability over Borneo Associated with ENSO
Authors: Qian Jian-Hua , Robertson Andrew W. , Moron Vincent 
Published: September 2012

Abstract
The interannual variability of precipitation over the island of Borneo in association with El Niño–Southern Oscillation (ENSO) has been studied by using the Global Precipitation Climatology Centre (GPCC) gridded rain gauge precipitation, the NOAA Climate Prediction Center (CPC) Morphing Technique (CMORPH) satellite estimated precipitation, the Quick Scatterometer (QuikSCAT) satellite estimated sea winds, and the National Centers for Environmental Prediction (NCEP)–National Center for Atmospheric Research (NCAR) reanalysis data. Analysis of the GPCC precipitation shows a dipolar structure of wet southwest versus dry central and northeast in precipitation anomalies associated with El Niño over Borneo Island during the austral summer [December–February (DJF)]. By using the 0.25° and 3-hourly CMORPH precipitation, it is found that rainfall over Borneo is strongly affected by the diurnal cycle of land–sea breezes. The spatial distribution of rainfall over Borneo depends on the direction of monsoonal winds. Weather typing analysis indicates that the dipolar structure of rainfall anomalies associated with ENSO is caused by the variability in the frequency of occurrence of different weather types. Rainfall is enhanced in the coastal region where sea breezes head against off-shore synoptic-scale low-level winds (i.e., in the lee side or wake area of the island), which is referred to here as the “wake effect.” In DJF of El Niño years, the northwesterly austral summer monsoon in southern Borneo is weaker than normal over the Maritime Continent and easterly winds are more frequent than normal over Borneo, acting to enhance rainfall over the southwest coast of the island. This coastal rainfall generation mechanism in different weather types explains the dipole pattern of a wet southwest versus dry northeast in the rainfall anomalies over Borneo Island in the El Niño years.
Metrics and Diagnostics for Precipitation-Related Processes in Climate Model Short-Range Hindcasts
Authors: Ma H.-Y. , Xie S. , Boyle J. S. , Klein S. A. , Zhang Y. 
Published: September 2012

Abstract
In this study, several metrics and diagnostics are proposed and implemented to systematically explore and diagnose climate model biases in short-range hindcasts and quantify how fast hindcast biases approach to climate biases with an emphasis on tropical precipitation and associated moist processes. A series of 6-day hindcasts with NCAR and the U.S. Department of Energy Community Atmosphere Model, version 4 (CAM4) and version 5 (CAM5), were performed and initialized with ECMWF operational analysis every day at 0000 UTC during the Year of Tropical Convection (YOTC). An Atmospheric Model Intercomparison Project (AMIP) type of ensemble climate simulations was also conducted for the same period. The analyses indicate that initial drifts in precipitation and associated moisture processes (“fast processes”) can be identified in the hindcasts, and the biases share great resemblance to those in the climate runs. Comparing to Tropical Rainfall Measuring Mission (TRMM) observations, model hindcasts produce too high a probability of low- to intermediate-intensity precipitation at daily time scales during northern summers, which is consistent with too frequently triggered convection by its deep convection scheme. For intense precipitation events (&gt;25 mm day−1), however, the model produces a much lower probability partially because the model requires a much higher column relative humidity than observations to produce similar precipitation intensity as indicated by the proposed diagnostics. Regional analysis on precipitation bias in the hindcasts is also performed for two selected locations where most contemporary climate models show the same sign of bias. Based on moist static energy diagnostics, the results suggest that the biases in the moisture and temperature fields near the surface and in the lower and middle troposphere are primarily responsible for precipitation biases. These analyses demonstrate the usefulness of these metrics and diagnostics to diagnose climate model biases.
Expansion of the Hadley Cell under Global Warming: Winter versus Summer
Authors: Kang Sarah M. , Lu Jian 
Published: September 2012

Abstract
A scaling relationship is introduced to explain the seasonality in the outer boundary of the Hadley cell in both climatology and trend in the simulations of phase 3 of the Coupled Model Intercomparison Project (CMIP3). In the climatological state, the summer cell reaches higher latitudes than the winter cell since the Hadley cell in summer deviates more from the angular momentum conserving state, resulting in weaker upper-level zonal winds, which enables the Hadley cell to extend farther poleward before becoming baroclinically unstable. The Hadley cell can also reach farther poleward as the ITCZ gets farther away from the equator; hence, the Hadley cell extends farther poleward in solstices than in equinoxes. In terms of trend, a robust poleward expansion of the Hadley cell is diagnosed in all seasons with global warming. The scaling analysis indicates this is mostly due to an increase in the subtropical static stability, which pushes poleward the baroclinically unstable zone and hence the poleward edge of the Hadley cell. The relation between the trends in the Hadley cell edge and the ITCZ is also discussed.