bluuebunny/crossref_metadata_2025_split huggingface dataset:
Soluble endoglin regulates expression of angiogenesis-related proteins and induction of arteriovenous malformations in a mouse model of hereditary hemorrhagic telangiectasia
Authors: Gallardo-Vara Eunate , Tual-Chalot Simon , Botella Luisa M. , Arthur Helen M. , Bernabeu Carmelo 
Published: August 2018

ABSTRACT
Endoglin is a transmembrane glycoprotein expressed in vascular endothelium that plays a key role in angiogenesis. Mutations in the endoglin gene (ENG) cause hereditary hemorrhagic telangiectasia type 1 (HHT1), characterized by arteriovenous malformations (AVMs) in different organs. These vascular lesions derive from abnormal processes of angiogenesis, whereby aberrant vascular remodeling leads to focal loss of capillaries. Current treatments for HHT1 include antiangiogenic therapies. Interestingly, a circulating form of endoglin (also known as soluble endoglin, sEng), proteolytically released from the membrane-bound protein and displaying antiangiogenic activity, has been described in several endothelial-related pathological conditions. Using human and mouse endothelial cells, we find that sEng downregulates several pro-angiogenic and pro-migratory proteins involved in angiogenesis. However, this effect is much reduced in endothelial cells that lack endogenous transmembrane endoglin, suggesting that the antiangiogenic activity of sEng is dependent on the presence of endogenous transmembrane endoglin protein. In fact, sEng partially restores the phenotype of endoglin-silenced endothelial cells to that of normal endothelial cells. Moreover, using an established neonatal retinal model of HHT1 with depleted endoglin in the vascular endothelium, sEng treatment decreases the number of AVMs and has a normalizing effect on the vascular phenotype with respect to vessel branching, vascular density and migration of the vascular plexus towards the retinal periphery. Taken together, these data show that circulating sEng can influence vascular development and AVMs by modulating angiogenesis, and that its effect on endothelial cells depends on the expression of endogenous endoglin.
This article has an associated First Person interview with the first author of the paper.
A Drosophila model of combined D-2- and L-2-hydroxyglutaric aciduria reveals a mechanism linking mitochondrial citrate export with oncometabolite accumulation
Authors: Li Hongde , Hurlburt Alexander J. , Tennessen Jason M. 
Published: August 2018

ABSTRACT
The enantiomers of 2-hydroxyglutarate (2HG) are potent regulators of metabolism, chromatin modifications and cell fate decisions. Although these compounds are associated with tumor metabolism and commonly referred to as oncometabolites, both D- and L-2HG are also synthesized by healthy cells and likely serve endogenous functions. The metabolic mechanisms that control 2HG metabolism in vivo are poorly understood. One clue towards how cells regulate 2HG levels has emerged from an inborn error of metabolism known as combined D- and L-2HG aciduria (D-/L-2HGA), which results in elevated D- and L-2HG accumulation. Because this disorder is caused by mutations in the mitochondrial citrate transporter (CIC), citrate must somehow govern 2HG metabolism in healthy cells. The mechanism linking citrate and 2HG, however, remains unknown. Here, we use the fruit fly Drosophila melanogaster to elucidate a metabolic link between citrate transport and L-2HG accumulation. Our study reveals that the Drosophila gene scheggia (sea), which encodes the fly CIC homolog, dampens glycolytic flux and restricts L-2HG accumulation. Moreover, we find that sea mutants accumulate excess L-2HG owing to elevated lactate production, which inhibits L-2HG degradation by interfering with L-2HG dehydrogenase activity. This unexpected result demonstrates that citrate indirectly regulates L-2HG stability and reveals a feedback mechanism that coordinates L-2HG metabolism with glycolysis and the tricarboxylic acid cycle. Finally, our study also suggests a potential strategy for preventing L-2HG accumulation in human patients with CIC deficiency.
This article has an associated First Person interview with the first author of the paper.
Neuromodulation influences synchronization and intrinsic read-out
Authors: Scheler Gabriele 
Published: August 2018

Background: The roles of neuromodulation in a neural network, such as in a cortical microcolumn, are still incompletely understood. Methods: (a) Neuromodulation influences neural processing by presynaptic and postsynaptic regulation of synaptic efficacy. Synaptic efficacy modulation can be an effective way to rapidly alter network density and topology. We show that altering network topology and density, will affect spike synchronization. Fast synaptic efficacy modulation may therefore influence the amount of correlated spiking in a network. (b) Neuromodulation also affects ion channel regulation for intrinsic excitability, which alters the neuron’s activation function. Results: We show that synchronization in a network influences the read-out of these intrinsic properties. Highly synchronous input drives neurons, such that differences in intrinsic properties disappear, while asynchronous input lets intrinsic properties determine output behavior. Thus, altering network topology can alter the balance between intrinsically vs. synaptically driven network activity. Conclusion: We conclude that neuromodulation may allow a network to shift between a more synchronized transmission mode and a more asynchronous intrinsic read-out mode. This has significant implications for our understanding of the flexibility of cortical computations.
Barriers to the use of facility-based birthing services in rural northern Ghana: A qualitative study
Authors: Nyefene Martin Kwabena , Ayanore Martin Amogre , Adatara Peter , Groot Wim , Pavlova Milena 
Published: August 2018

Background: Use of facility-based birthing can reduce maternal mortality rates; however, service uptake is still poor in rural Ghana. Aims: To analyse key stakeholders' views on barriers to facility-based birthing in the Bongo district of rural northern Ghana. Methods: The study used a qualitative design. A purposive sampling technique was used to recruit 45 women from three communities for the study, plus four health professionals and two policy-makers. Data were collected through in-depth interviews and focus group discussions. Findings: This study revealed major barriers to the use of facility-based birthing services, including an inability to pay for transport and items for childbirth, poor quality of services, impolite staff, long distance, and the influence of significant others. Health professionals and policy-makers identified staff/facility inadequacy and general logistic constraints as major barriers. Conclusions: Women should be empowered through education campaigns, a review of the health insurance scheme and realignment of the facility protocols.
Universal meaning extensions of perception verbs are grounded in interaction
Authors: San Roque Lila , Kendrick Kobin H. , Norcliffe Elisabeth , Majid Asifa 
Published: August 2018

AbstractApart from references to perception, words such asseeandlistenhave shared, non-literal meanings across diverse languages. Such cross-linguistic meanings have not been systematically investigated as they appear in their natural home — informal spoken interaction. We present a qualitative examination of the semantic associations of perception verbs based on recorded everyday conversation in thirteen diverse languages. Across these diverse communities, spontaneous interaction provides evidence for two commonly-discussed extensions of perception verbs — perception~cognition, hearing~linguistic communication — as well as illustrating other meanings and functions (e.g., the use of perception verbs as discourse markers) that have been less appreciated heretofore. The range of usage that is readily observable in informal conversation makes it clear that this type of data must take center stage for the empirically grounded study of semantics. Moreover, these data suggest that commonalities in polysemous meanings may rely not only on universal cognition, but also on the universal exigencies of social interaction.
The gene expression and enzymatic activity of pinoresinol-lariciresinol reductase during wood formation in Taiwania cryptomerioides Hayata
Authors: Chiang Nien-Ting , Ma Li-Ting , Lee Yi-Ru , Tsao Nai-Wen , Yang Chih-Kai , Wang Sheng-Yang , Chu Fang-Hua 
Published: August 2018

Abstract
Taiwania (Taiwania cryptomerioides Hayata) is an indigenous conifer species of Taiwan. Various secondary metabolites of Taiwania with diverse bioactivities have been identified, and lignans are especially abundant in the heartwood (hW). In the present study, the wood of this species was separated to cambium (Cam), sapwood (sW), transition zone (TZ) and hW and their transcriptomes were sequenced. Three pinoresinol-lariciresinol reductases (PLRs; designated TcPLR1, TcPLR2.2 and TcPLR3), which are responsible for lignan biosynthesis, were cloned and their expressions in wood tissues were detected. TcPLRs had higher expression levels in Cam and sW in RNA-seq and reverse transcriptase-polymerase chain reaction (RT-PCR) results. Liquid chromatography-mass spectrometry (LC-MS) analysis of the reaction products of TcPLRs revealed that TcPLR1 can reduce (+)-pinoresinol to lariciresinol, and both TcPLR2.2 and TcPLR3 could reduce (+)-pinoresinol to lariciresinol and secoisolariciresinol.
Long-term medical data storage: challenges with test results obtained by direct-to-consumer testing
Authors: Orth Matthias , Bühling Frank , Hoffmann Georg 
Published: August 2018

AbstractThe term “direct-to-consumer testing” (DTCT) describes all kinds of laboratory testing performed without the inclusion of a laboratory professional. It is thus performed in a gray zone between healthcare and consumers. The high volume of DTCT data as well as the ostensible feasibility of long-term data storage challenge medical professionals and consumers. No standards have been developed so far for the long-term storage of DTCT data. Unlike tests used in traditional laboratory medicine, many DTCT tests lack medical usefulness. This article describes the current concepts of DTCT and gives recommendations for the long-term data storage of DTCT data depending on the purpose of DTCT, the volume of data obtained and the possible medical implications of the test results.
Correlation between Structural, Magnetic and Spectroscopic Properties of Mg Substituted CoFe2O4
Authors: Nethala Gnana Praveena , Tadi Ravindar , Anupama Aroli Venkateswara , Shinde Satish Laxman , Veeraiah V. 
Published: August 2018

AbstractMg substituted cobalt ferrite spinel powder samples with the general formula MgxCO1-xFe2O4(x = 0 to 0.25) were synthesized chemically through sol-gel method and annealed at 1100 °C for 2 h. They were initially screened for the structural and morphological properties by X-ray diffraction and field emission scanning electron microscopy, respectively. Vibrational properties of the samples were studied by Raman and infrared spectroscopies. X-ray diffraction confirmed the formation of single pure or near-pure phase with cubic spinel structure for all the samples with expected occupancy values. The field emission scanning electron microscopy revealed a decrease in the particle size with an increase in Mg concentration. Both structural and magnetic properties of the samples were characterized using Mössbauer spectroscopy while the magnetic properties were studied using vibrating sample magnetometry. The changes in magnetic moment of ions, their coupling with neighboring ions and cation exchange interactions were confirmed from the Mössbauer spectroscopy analysis. Saturation magnetization and coercivity values can be explained based on the Slater-Pauling curve. The magnetometry results showed a decrease in saturation magnetization of the samples with increase in Mg concentration
A unified framework jointly explaining business conditions, stock returns, volatility and “volatility feedback news” effects
Authors: Kim Chang-Jin , Kim Yunmi 
Published: August 2018

AbstractOne of central questions to macroeconomics and finance has been whether macroeconomic factors are useful predictors for expected stock returns. The general consensus is somewhat surprising in that financial factors, rather than macroeconomic factors, have predictive power on stock returns. Such predictability of financial factors is justified on the ground that those factors can act as a proxy for future business conditions and undiversifiable risk. Hence, they should be priced in terms of expected returns. However, as suggested by Campbell, S., and F. Diebold. 2009. “Stock Returns and Expected Business Conditions: Half a Century of Direct Evidence.”Journal of Business & Economic Statistics27 (2): 266–278, such a justification can be puzzling because macroeconomic factors are likely to have a closer and more direct link to future business conditions than financial factors. In this paper, we will attempt to solve this puzzling problem by accounting for market volatility when measuring the relationship between stock returns and macroeconomic factors. As a result, we propose a unified framework in which the three components of macroeconomic factors, market volatility, and stock returns are jointly embedded.
Test Method Evaluation and Model Development for Erodibility Properties of Cementitiously Stabilized Layers
Authors: Wang Jingan , Wen Haifang , Muhunthan Balasingam 
Published: August 2018

Abstract
Cementitiously stabilized layers (CSL) have been used extensively by highway agencies over the years. The erosion of CSL can cause several distresses in flexible and rigid pavements. The three necessary conditions for the occurrence of erosion are heavy loads, sufficient moisture, and the presence of erodible materials. The Mechanistic-Empirical Pavement Design Guide (MEPDG) provides a methodology for the analysis and performance prediction of pavements that incorporate CSL. However, test methods and models that specifically address the erosion of CSL have not yet been incorporated into the MEPDG. This study evaluates the existing test methods for erosion, including wheel tracking, manual wet-dry brushing, rotational shear device (RSD), jetting, a vibration table, or cyclic impact erosion (CIE), or combinations thereof. It is found that a CIE test is a robust test procedure that is used to quantify the erodibility of CSL. Based on the laboratory results from a CIE test, an empirical model that combines top-down compressive fatigue and erosion is developed to predict the erodibility of CSL. It is found that the developed model is effective in predicting both the top-down compressive fatigue and erosion of CSL. This test method and prediction model are recommended for incorporation into the MEPDG.
Estimation of Service Life of Geosynthetic-Reinforced Asphalt Overlays from Beam and Large-Scale Fatigue Tests
Authors: Saride Sireesh , Kumar V. Vinay 
Published: August 2018

Abstract
In this study, an attempt has been made to develop a model to predict the service life of geosynthetic-reinforced hot mix asphalt (HMA) overlay placed over distressed pavements based on fatigue behavior observed in beam and large-scale tests. A two-stage detailed experimental program was designed to understand the fatigue behavior and reinforcement effects of asphalt overlays reinforced with geosynthetic interlayers. During the first stage, small-scale beam flexural fatigue tests were conducted on the HMA overlays to understand the reflection cracking and deformation behaviors with the aid of digital image correlation (DIC) techniques. During the second stage, the fatigue behavior of overlays was evaluated under repeated load tests on large-scale pavement sections built over a weak subgrade in a large test tank. Two types of geosynthetic interlayers, namely, polyester grid coated with polymer modified binder (PE) and a glass-grid composite (GGC) with different tensile strength and strain characteristics, were employed. The beam flexural fatigue test results along with DIC data indicated that the geosynthetic-interlayers have effectively minimized the crack propagation into overlays even under unconfined conditions. Whereas, for the same permanent deformation, the large-scale test sections sustained a higher number of load repetitions, reaching 100-fold, because of the presence of a base course structural support. A simple model to estimate the service life of the geosynthetic asphalt overlays has been proposed based on the beam fatigue tests viz. normalized complex modulus × cycles and a corresponding number of load repetitions for a prescribed rutting. Overall, for a vertical deformation of about 7.5 mm, it is estimated that GGC and PE interlayers would give a service life of 4.1 and 2.9 years, respectively, in real field scenarios.
Prospective Analysis of the Effects of Maternal Immune Activation on Rat Cytokines during Pregnancy and Behavior of the Male Offspring Relevant to Schizophrenia
Authors: Lins Brittney R. , Hurtubise Jessica L. , Roebuck Andrew J. , Marks Wendie N. , Zabder Nadine K. , Scott Gavin A. , Greba Quentin , Dawicki Wojciech , Zhang Xiaobei , Rudulier Christopher D. , Gordon John R. , Howland John G. 
Published: August 2018

AbstractInfluenza during pregnancy is associated with the development of psychopathology in the offspring. We sought to determine whether maternal cytokines produced following administration of viral mimetic polyinosinic-polycytidylic acid (polyI:C) to pregnant rats were predictive of behavioral abnormalities in the adult offspring. Timed-pregnant Sprague Dawley rats received a single intravenous injection of 4-mg/kg polyI:C or saline on gestational day (GD)15. Blood was collected 3 h later for serum analysis of cytokine levels with ELISA. Male offspring were tested in a battery of behavioral tests during adulthood and behavior was correlated with maternal cytokine levels. Maternal serum levels of CXCL1 and interleukin (IL)-6, but not tumor necrosis factor (TNF)-α or CXCL2, were elevated in polyI:C-treated dams. PolyI:C-treated dams experienced post-treatment weight loss and polyI:C pups were smaller than controls at postnatal day (PND)1. Various behavior alterations were seen in the polyI:C-treated offspring. Male polyI:C offspring had enhanced MK-801-induced locomotion, and reduced sociability. PolyI:C offspring failed to display crossmodal and visual memory, and oddity preference was also impaired. Set-shifting, assessed with a lever-based operant conditioning task, was facilitated while touchscreen-based reversal learning was impaired. Correlations were found between maternal serum concentrations of CXCL1, acute maternal temperature and body weight changes, neonatal pup mass, and odd object discrimination and social behavior. Overall, while the offspring of polyI:C-treated rats displayed behavior abnormalities, maternal serum cytokines were not related to the long-term behavior changes in the offspring. Maternal sickness effects and neonatal pup size may be better indicators of later effects of maternal inflammation in the offspring.
Interneuron Simplification and Loss of Structural Plasticity As Markers of Aging-Related Functional Decline
Authors: Eavri Ronen , Shepherd Jason , Welsh Christina A. , Flanders Genevieve H. , Bear Mark F. , Nedivi Elly 
Published: August 2018

Changes in excitatory neuron and synapse structure have been recognized as a potential physical source of age-related cognitive decline. Despite the importance of inhibition to brain plasticity, little is known regarding aging-associated changes to inhibitory neurons. Here we test for age-related cellular and circuit changes to inhibitory neurons of mouse visual cortex. We find no substantial difference in inhibitory neuron number, inhibitory neuronal subtypes, or synapse numbers within the cerebral cortex of aged mice compared with younger adults. However, when comparing cortical interneuron morphological parameters, we find differences in complexity, suggesting that arbors are simplified in aged mice.In vivotwo-photon microscopy has previously shown that in contrast to pyramidal neurons, inhibitory interneurons retain a capacity for dendritic remodeling in the adult. We find that this capacity diminishes with age and is accompanied by a shift in dynamics from balanced branch additions and retractions to progressive prevalence of retractions, culminating in a dendritic arbor that is both simpler and more stable. Recording of visually evoked potentials shows that aging-related interneuron dendritic arbor simplification and reduced dynamics go hand in hand with loss of induced stimulus-selective response potentiation (SRP), a paradigm for adult visual cortical plasticity. Chronic treatment with the antidepressant fluoxetine reversed deficits in interneuron structural dynamics and restored SRP in aged animals. Our results support a structural basis for age-related impairments in sensory perception, and suggest that declines in inhibitory neuron structural plasticity during aging contribute to reduced functional plasticity.SIGNIFICANCE STATEMENTStructural alterations in neuronal morphology and synaptic connections have been proposed as a potential physical basis for age–related decline in cognitive function. Little is known regarding aging-associated changes to inhibitory neurons, despite the importance of inhibitory circuitry to adult cortical plasticity and the reorganization of cortical maps. Here we show that brain aging goes hand in hand with progressive structural simplification and reduced plasticity of inhibitory neurons, and a parallel decline in sensory map plasticity. Fluoxetine treatment can attenuate the concurrent age–related declines in interneuron structural and functional plasticity, suggesting it could provide an important therapeutic approach for mitigating sensory and cognitive deficits associated with aging.
Reduced slow-wave sleep and altered diurnal cortisol rhythms in patients with Addison’s disease
Authors: Henry Michelle , Ross Ian Louis , Thomas Kevin Garth Flusk 
Published: August 2018

ObjectivesCortisol plays a key role in initiating and maintaining different sleep stages. Patients with Addison’s disease (AD) frequently report disrupted sleep, and their hydrocortisone medication regimes do not restore the natural diurnal rhythm of cortisol. However, few studies have investigated relations between sleep quality, especially as measured by polysomnographic equipment, and night-time cortisol concentrations in patients with AD.MethodsWe used sleep-adapted EEG to monitor a full night of sleep in seven patients with AD and seven healthy controls. We sampled salivary cortisol before bedtime, at midnight, upon awakening and at 30 min post waking.ResultsControls had lower cortisol concentrations than patients before bedtime and at midnight. During the second half of the night, patient cortisol concentrations declined steeply, while control concentrations increased steadily. Whereas most controls experienced a positive cortisol awakening response, all patients experienced a decrease in cortisol concentrations from waking to 30 min post waking (P = 0.003). Patients experienced significantly lower proportions of slow-wave sleep (SWS;P = 0.001), which was associated with elevated night-time cortisol concentrations.ConclusionOverall, these results suggest that patients with AD demonstrate different patterns of night-time cortisol concentrations to healthy controls and that relatively elevated concentrations are associated with a reduction of SWS. These hormonal and sleep architectural aberrations may disrupt the routine sleep-dependent processes of memory consolidation, and hence, may explain, at least partially, the memory impairments often experienced by patients with AD.