bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD73 Promotes Age-Dependent Accretion of Atherosclerosis
Authors: Sutton Nadia R. , Bouïs Diane , Mann Kris M. , Rashid Imran M. , McCubbrey Alexandra L. , Hyman Matt C. , Goldstein Daniel R. , Mei Annie , Pinsky David J. 
Published: October 2019

Objective:
CD73 is an ectonucleotidase which catalyzes the conversion of AMP (adenosine monophosphate) to adenosine. Adenosine has been shown to be anti-inflammatory and vasorelaxant. The impact of ectonucleotidases on age-dependent atherosclerosis remains unclear. Our aim was to investigate the role of CD73 in age-dependent accumulation of atherosclerosis.

Approach and results:

Mice doubly deficient in CD73 and ApoE (apolipoprotein E; (

cd73
−
/−
/apoE
−/−

) were generated, and the extent of aortic atherosclerotic plaque was compared with

apoE
−/−

controls at 12, 20, 32, and 52 weeks. By 12 weeks of age,

cd73
−/−
/apoE
−/−

mice exhibited a significant increase in plaque (1.4±0.5% of the total vessel surface versus 0.4±0.1% in

apoE
−/−

controls,
P
<0.005). By 20 weeks of age, this difference disappeared (2.9±0.4% versus 3.3±0.7%). A significant reversal in phenotype emerged at 32 weeks (9.8±1.2% versus 18.3±1.4%;
P
<0.0001) and persisted at the 52 week timepoint (22.4±2.1% versus 37.0±2.1%;
P
<0.0001). The inflammatory response to aging was found to be comparable between

cd73
−/−
/apoE
−/−

mice and

apoE
−/−

controls. A reduction in lipolysis in CD73 competent mice was observed, even with similar plasma lipid levels (

cd73
−/−
/apoE
−/−

versus

apoE
−/−

at 12 weeks [16.2±0.7 versus 9.5±1.4 nmol glycerol/well], 32 weeks [24.1±1.5 versus 7.4±0.4 nmol/well], and 52 weeks [13.8±0.62 versus 12.7±2.0 nmol/well],
P
<0.001).

Conclusions:
At early time points, CD73 exerts a subtle antiatherosclerotic influence, but with age, the pattern reverses, and the presence of CD73 promoted suppression of lipid catabolism.
Spectrum of Mutations and Long-Term Clinical Outcomes in Genetic Chylomicronemia Syndromes
Authors: D’Erasmo Laura , Di Costanzo Alessia , Cassandra Francesca , Minicocci Ilenia , Polito Luca , Montali Anna , Ceci Fabrizio , Arca Marcello 
Published: October 2019

Objective:
Familial chylomicronemia syndrome (FCS) and multifactorial chylomicronemia syndrome (MCS) are the prototypes of monogenic and polygenic conditions underlying genetically based severe hypertriglyceridemia. These conditions have been only partially investigated so that a systematic comparison of their characteristics remains incomplete. We aim to compare genetic profiles and clinical outcomes in FCS and MCS.

Approach and Results:

Thirty-two patients with severe hypertriglyceridemia (triglyceride >1000 mg/dL despite lipid-lowering treatments with or without history of acute pancreatitis) were enrolled. Rare and common variants were screened using a panel of 18 triglyceride-raising genes, including the canonical
LPL
,
APOC2
,
APOA5
,
GP1HBP1
, and
LMF1
. Clinical information was collected retrospectively for a median period of 44 months. Across the study population, 37.5% were classified as FCS due to the presence of biallelic, rare mutations and 59.4% as MCS due to homozygosity for nonpathogenic or heterozygosity for pathogenic variants in canonical genes, as well as for rare and low frequency variants in noncanonical genes. As compared with MCS, FCS patients showed a lower age of hypertriglyceridemia onset, higher levels of on-treatment triglycerides, and 3-fold higher incidence rate of acute pancreatitis.

Conclusions:

Our data indicate that the genetic architecture and natural history of FCS and MCS are different. FCS expressed the most severe clinical phenotype as determined by resistance to triglyceride-lowering medications and higher incidence of acute pancreatitis episodes. The most common genetic abnormality underlying FCS was represented by biallelic mutations in
LPL
while
APOA5
variants, in combination with high rare polygenic burden, were the most frequent genotype of MCS.
Association Between High Perceived Stress Over Time and Incident Hypertension in Black Adults: Findings From the Jackson Heart Study
Authors: Spruill Tanya M. , Butler Mark J. , Thomas S. Justin , Tajeu Gabriel S. , Kalinowski Jolaade , Castañeda Sheila F. , Langford Aisha T. , Abdalla Marwah , Blackshear Chad , Allison Matthew , Ogedegbe Gbenga , Sims Mario , Shimbo Daichi 
Published: October 2019

Background
Chronic psychological stress has been associated with hypertension, but few studies have examined this relationship in blacks. We examined the association between perceived stress levels assessed annually for up to 13 years and incident hypertension in the Jackson Heart Study, a community‐based cohort of blacks.

Methods and Results

Analyses included 1829 participants without hypertension at baseline (Exam 1, 2000–2004). Incident hypertension was defined as blood pressure≥140/90 mm Hg or antihypertensive medication use at Exam 2 (2005–2008) or Exam 3 (2009–2012). Each follow‐up interval at risk of hypertension was categorized as low, moderate, or high perceived stress based on the number of annual assessments between exams in which participants reported “a lot” or “extreme” stress over the previous year (low, 0 high stress ratings; moderate, 1 high stress rating; high, ≥2 high stress ratings). During follow‐up (median, 7.0 years), hypertension incidence was 48.5%. Hypertension developed in 30.6% of intervals with low perceived stress, 34.6% of intervals with moderate perceived stress, and 38.2% of intervals with high perceived stress. Age‐, sex‐, and time‐adjusted risk ratios (95% CI) associated with moderate and high perceived stress versus low perceived stress were 1.19 (1.04–1.37) and 1.37 (1.20–1.57), respectively (
P
trend<0.001). The association was present after adjustment for demographic, clinical, and behavioral factors and baseline stress (
P
trend=0.001).

Conclusions
In a community‐based cohort of blacks, higher perceived stress over time was associated with an increased risk of developing hypertension. Evaluating stress levels over time and intervening when high perceived stress is persistent may reduce hypertension risk.
Abstract 478: Identifying Signaling Pathways Regulated by Trophoblasts in Placental Vascular Development Using 3D Tissue Models
Authors: Kashpur Olga , Wallingford Mary C 
Published: October 2019

The placenta is an essential yet transient organ that supports healthy pregnancy and normal fetal development. Placental vascular dysfunction is associated with preeclampsia, HELLP (hemolysis, elevated liver enzymes, low platelets), fetal growth restriction, hemorrhaging, preterm birth, and loss of life. Placental vascular dysfunction can also negatively impact long-term maternal and offspring health, increasing risk for cardiovascular disease, coronary artery calcification, and stroke later in life.
The vasculature of the maternal-fetal interface is uniquely characterized by the presence of trophoblast cells. Multiple trophoblast cell lineages serve essential functions in both the maternal vascular compartment and the feto-placental angioarchitecture. Functional roles for FGF2, VEGF, and angiopoietin signaling pathways in endothelial vasculogenesis and angiogenesis are well supported by a large body of literature, but there is a gap in knowledge of placenta-specific molecular mechanisms that account for the unique interaction of trophoblasts and endothelial cells. I hypothesize that trophoblasts generate angiogenic signals that promote vascular development at the maternal-fetal interface in both an autocrine and paracrine manner.
Using 3D assays, I evaluated the role of endovascular cytotrophoblast and syncytiotrophoblast cell lines in establishment of a vascular compartment. Trophoblasts harbor intrinsic angiogenic competency evident by their ability to form angiogenic sprouts and generate 3D vascular networks under defined conditions. My current research implements 3D bioassays, bio-engineered vessels, and chemical inhibition to further investigate paracrine angiogenic signaling between trophoblasts and endothelial cells.
Our work is the first to evaluate autocrine and paracrine angiogenic properties of trophoblasts under physiological 3D conditions that mimic development. When coupled with histological evaluation of human placenta, these systems will allow us to better evaluate and understand molecular mechanisms of placental vascular development and vascular dysfunction.
Abstract 781: Doxorubicin-Induced Cardiotoxicity and Novel GATA4-Targeted Compounds
Authors: Karhu Tuuli , Kinnunen Sini , Talman Virpi , Ruskoaho Heikki 
Published: October 2019

Doxorubicin (DOX) is a widely used anticancer drug which, unfortunately, induces dose-related cardiotoxicity. A deep understanding of DOX’s toxicity is still unclear, partly because most
in vitro
studies have evaluated the effects of short-term high-dose DOX treatments. Thus, a more precise model of DOX cardiotoxicity is needed to more accurately simulate clinical scenario.

The first aim of this study was to establish an
in vitro
model of long-term low-dose administration of DOX utilizing human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The second aim was to investigate if novel GATA4-targeted compounds can protect CMs from DOX toxicity.

Acute toxicity was studied in both primary neonatal rat ventricular cardiomyocytes (NRVCs) and hiPSC-CMs. The cells were exposed to 0.1-3 μM DOX for 48 h, after which the lactate dehydrogenase and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were carried out. To study long-term toxicity, hiPSC-CMs were exposed to 100 nM DOX for up to 14 days. MTT assay and high-content analysis were carried out after 4, 7 and 14-day exposures. The effect of the test compound was studied by exposing the cells simultaneously to DOX and the compound.
A 48-hour exposure to DOX at 1 and 3 μM concentrations induced more than 62% reductions in both NRVC and hiPSC-CM viability, whereas a 14-day exposure to 100 nM DOX induced a 26% reduction in hiPSC-CM viability. A 4-day exposure to 100 nM DOX induced a 3.1-fold increase in the percentage of cells positive for pro-B-type natriuretic peptide (proBNP) compared to control. When the cells were exposed simultaneously to 100 nM DOX and the test compound (10 μM), the percentage of proBNP+ cells increased only 1.4-fold compared to control. However, over 14-day exposure the compound at 10 μM concentration reduced hiPSC-CM viability 50% compared to control.

A long-term exposure of hiPSC-CMs can be utilized as an
in vitro
model to investigate the mechanisms of delayed DOX-induced cardiotoxicity. The GATA4-targeted test compound exhibited cardioprotective potential against subacute DOX toxicity. Over chronic exposure the compound was, however, toxic to CMs, indicating that further structural optimization is required to develop non-toxic derivatives.
Abstract 850: Metabolic Landscape of Human Heart Failure
Authors: Flam Emily , Jang Cholsoon , Bedi Kenneth , Margulies Kenneth , Arany Zoltan 
Published: October 2019

Heart failure is characterized by insufficient pumping to match the needs of the body. Heart failure is thought to be associated with dysfunctional mitochondria and metabolic alterations, but there is little to no direct evidence in humans. The heart metabolizes a variety of substrates for energy production, including fatty acids, glucose, ketones, and branch chain amino acids (BCAAs). In the healthy heart, fatty acids are the main fuel source, and oxidation is balanced with energy need. In heart failure, it is asserted that fatty acid oxidation is suppressed, and glucose utilization is increased, but this has not been directly measured in humans. If true, this metabolic switch toward glucose may contribute to mechanical insufficiency by disrupting the balance between metabolism and energetic need, thus representing a potential area for therapeutic intervention in heart failure. Prior studies were largely performed in animal models, and results are often inconsistent across models and species. Challenges have constrained the use of human myocardium, including costly and cumbersome techniques for in vivo assessment; limited availability of high-quality human myocardial tissue; and low yields and short durability of isolated human cardiomyocytes. We addressed these challenges by taking advantage of human explanted hearts available via the Penn Heart Transplant program to investigate the metabolic differences between failing and healthy human hearts.
We performed metabolomics analysis using mass spectrometry on myocardium from 18 failing and 20 nonfailing human hearts. Of the 334 metabolites measured, 99 were significantly different between groups by Wilcoxon test and FDR correction. Metabolite set enrichment analysis revealed that the most enriched pathways included the glycerol phosphate shuttle, ammonia recycling, methylhistidine metabolism, and glutathione metabolism. The mitochondrial electron transport chain, BCAA catabolism, purine metabolism, the urea cycle, gluconeogenesis, glycolysis, ketone body metabolism, and the pentose phosphate pathway were also included in the top 50 most enriched pathways. These data will guide future targeted metabolic studies in human heart failure.
NON-STOP FLIGHTS AND EXPORTS: TURKISH EXPERIENCE
Authors: KAL Süleyman 
Published: October 2019

The relationship between direct flights has attracted attention in the literature. Case in point Turkish Airlines opened many new routes between the years 1998 and 2015. In this paper, we investigated impact of airline flight on export. To achieve this, using 51 first time destinations of Turkish Airlines, which opened 145 new destinations between 1998 and 2015, impact of direct flight on exports is analyzed by controlling bilateral real exchange rates and GDP with a panel data method accounting for endogeneity (using Arnello Bond method) between direct international flights and exports. Results suggest each additional first time direct flight increases the exports to those destinations by 12.7 %.
Ventriloquist Illusion Produced With Virtual Acoustic Spatial Cues and Asynchronous Audiovisual Stimuli in Both Young and Older Individuals
Authors: Stawicki Marnix , Majdak Piotr , Başkent Deniz 
Published: October 2019

Abstract
Ventriloquist illusion, the change in perceived location of an auditory stimulus when a synchronously presented but spatially discordant visual stimulus is added, has been previously shown in young healthy populations to be a robust paradigm that mainly relies on automatic processes. Here, we propose ventriloquist illusion as a potential simple test to assess audiovisual (AV) integration in young and older individuals. We used a modified version of the illusion paradigm that was adaptive, nearly bias-free, relied on binaural stimulus representation using generic head-related transfer functions (HRTFs) instead of multiple loudspeakers, and tested with synchronous and asynchronous presentation of AV stimuli (both tone and speech). The minimum audible angle (MAA), the smallest perceptible difference in angle between two sound sources, was compared with or without the visual stimuli in young and older adults with no or minimal sensory deficits. The illusion effect, measured by means of MAAs implemented with HRTFs, was observed with both synchronous and asynchronous visual stimulus, but only with tone and not speech stimulus. The patterns were similar between young and older individuals, indicating the versatility of the modified ventriloquist illusion paradigm.
Rotating One’s Head Modulates the Perceived Velocity of Motion Aftereffect
Authors: Bai Jianying , He Xin , Jiang Yi , Zhang Tao , Bao Min 
Published: October 2019

Abstract
As a prominent illusion, the motion aftereffect (MAE) has traditionally been considered a visual phenomenon. Recent neuroimaging work has revealed increased activities in MT+ and decreased activities in vestibular regions during the MAE, supporting the notion of visual–vestibular interaction on the MAE. Since the head had to remain stationary in fMRI experiments, vestibular self-motion signals were absent in those studies. Accordingly, more direct evidence is still lacking in terms of whether and how vestibular signals modulate the MAE. By developing a virtual reality approach, the present study for the first time demonstrates that horizontal head rotation affects the perceived velocity of the MAE. We found that the MAE was predominantly perceived as moving faster when its direction was opposite to the direction of head rotation than when its direction was the same as head rotation. The magnitude of this effect was positively correlated with the velocity of head rotation. Similar result patterns were not observed for the real motion stimuli. Our findings support a ‘cross-modal bias’ hypothesis that after living in a multisensory environment long-term the brain develops a strong association between signals from the visual and vestibular pathways. Consequently, weak biasing visual signals in the associated direction can spontaneously emerge with the input of vestibular signals in the multisensory brain areas, substantially modulating the illusory visual motion represented in those areas as well. The hypothesis can also be used to explain other multisensory integration phenomena.
Martial Identities in Colonial Nigeria (c. 1900–1960)
Authors: Stapleton Timothy J. 
Published: October 2019

Abstract
In British colonial Nigeria, the military was more heterogeneous than previously thought and British ideas about “martial races” changed depending on local reactions to recruiting. In the early twentieth century British officers saw the northern Hausa and southwestern Yoruba, who dominated the ranks, as civilized “martial races.” The Yoruba stopped enlisting given new prospects and protest, and southeasterners like the Igbo rejected recruiting given language difficulties and resistance. The British then perceived all southern Nigerians as lacking martial qualities. Although Hausa enlistment also declined with opportunities and religious objections, the inter-war army developed a northern ethos through Hausa language and the northern location of military institutions. The rank-and-file became increasingly diverse including northern and Middle Belt minorities, seen by the British as primitive warriors and as insurance against Muslim revolt, enlisting because of poverty. From 1930, military identities in Nigeria polarized with uneducated northern/Middle Belt infantry and literate southern technicians.
Climate Warming Changed the Planting Boundaries of Varieties of Summer Corn with Different Maturity Levels in the North China Plain
Authors: Hu Qi , Ma Xueqing , Pan Xuebiao , Binxiang Huang 
Published: October 2019

AbstractClimate warming in the North China Plain (NCP) is expected to greatly affect corn production. On the basis of a comprehensive consideration of the double-cropping system, we investigated the impacts of climate warming in the past 55 years on the planting boundaries and areas of varieties of summer corn with different maturity levels. In addition, we tried to explore the probable reasons for the changes in planting boundaries. Climate warming caused a northward shift in the planting boundaries of summer corn, resulting in the expansion of the total planting area. However, the trend for the planting area of each belt of corn maturity was not always consistent. Because of the advanced planting date and delayed physiological maturation date, the growing season of corn in the NCP has been prolonged in the past 55 years. Climate warming also increased the active accumulated temperature with a threshold of 10° (AAT10) during the corn growing season by 73.2°C decade−1, which was mainly caused by the increase in the number of days with a daily temperature over 10°C. In summary, the planting boundaries of varieties of summer corn with different maturity levels have greatly changed due to climate change, and corn production in the NCP could benefit from climate warming through the greater planting area and longer growing season.
Effect of Warm SST in the Subtropical Eastern North Pacific on Triggering the Abrupt Change of the Mei-Yu Rainfall over South China in the Early 1990s
Authors: Wu Yi-Kai , Huang An-Yi , Wu Chia-Kai , Hong Chi-Cherng , Chang Chi-Chun 
Published: October 2019

AbstractIn the early 1990s, the mei-yu rainfall over South China in early boreal summer exhibited an abrupt change and northward extension. This change altered the pattern of East Asian summer rainfall from a dipole-like to a monopole-like pattern; that is, the out-of-phase relationship between the rainfall in the south and that in the north of the Yangtze and Huaihe River valley changed to an in-phase relationship. The physical processes potentially responsible for triggering this abrupt change were analyzed in this study. Our observations revealed that the western North Pacific subtropical high (WNPSH), sea surface temperature (SST) in the subtropical eastern North Pacific (SENP), and the mei-yu rainfall in South China exhibited an abrupt increase in the early 1990s, suggesting that these factors are correlated. From the observations and results of numerical experiments, we proposed that the abrupt SST warming in the SENP in the early 1990s generated an east–west overturning circulation anomaly in the Pacific Ocean and that the anomalous downward motion in the western North Pacific consequently triggered the abrupt increase and westward extension of the WNPSH in the early 1990s. The enhanced and westward extension of WNPSH created a low-level southeasterly anomaly that transported considerable humid and warm air into East Asia and sequentially triggered the abrupt increase of mei-yu rainfall in the South China in the early 1990s.
Assessment of Three Common Methods for Estimating Terrestrial Water Storage Change with Three Reanalysis Datasets
Authors: Deng Shanshan , Liu Suxia , Mo Xingguo 
Published: October 2019

AbstractTerrestrial water storage change (TWSC) plays a crucial role in the hydrological cycle and climate system. To date, methods including 1) the terrestrial water balance method (PER), 2) the combined atmospheric and terrestrial water balance method (AT), and 3) the summation method (SS) have been developed to estimate TWSC, but the accuracy of these methods has not been systematically compared. This paper compares the spatial and temporal differences of the TWSC estimates by the three methods comprehensively with the GRACE data during the 2002–13 period. To avoid the impact of different inputs in the comparison, three advanced reanalysis datasets are used, namely 1) the National Centers for Environmental Prediction (NCEP)–Department of Energy (DOE) Reanalysis II (NCEP R2), 2) the ECMWF interim reanalysis (ERA-Interim), and 3) the Japanese 55-Year Reanalysis (JRA-55). The results show that all estimates with PER and AT considerably overestimate the long-term mean on a regional scale because the data assimilation in the reanalysis opens the water budget. The difficulty of atmospheric observation and simulation in arid and polar tundra regions is the documented reason for the failure of the AT method to represent the TWSC phase over 30% of the region found in this study. Although the SS result exhibited the best overall agreement with GRACE, the amplitude of TWSC based on SS differed substantially from that of GRACE and the similarity coefficient of the global distribution between the SS-derived estimate and GRACE is still not high. More detailed considerations of groundwater and human activities, for example, irrigation and reservoir impoundments, can help SS to achieve a higher accuracy.