bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing Marine Nitrogen Cycle Rates and Process Sensitivities With a Global 3‐D Inverse Model
Authors: Martin T. S. , Primeau F. , Casciotti K. L. 
Published: August 2019

AbstractWe present results from a global inverse marine nitrogen (N) cycle model that include nitrate (NO3−) and nitrite (NO2−) concentrations and their N isotopic compositions as constraints on N cycle process rates in marine oxygen deficient zones (ODZs). NO2− is an important intermediate in the N cycle, particularly in ODZs where it is a substrate in the N loss processes, denitrification, and anammox. Similar to earlier work, our model yields a total water column N loss rate of 61 ± 10 Tg N/year. However, by including NO2− and its N isotopic composition, we are able to assess the relative contributions of denitrification and anammox to N loss and examine some of the potential drivers of that balance. We find that anammox contributes 60% of global water column N loss, dominating N loss along the edges of ODZs, while denitrification is more important in the anoxic ODZ cores. The decoupling of anammox and denitrification is supported by NO2− oxidation, which co‐occurs with NO3− reduction and anammox in ODZs. High rates of NO2− oxidation (up to 400 nM/day), which are tightly coupled to heterotrophic NO3− reduction, are required to match NO3− and NO2− concentration and isotope observations in marine ODZs. Lowering the rate of NO2− oxidation in ODZs by adjusting O2‐sensitive parameters results in higher rates of water column N loss, highlighting the role of NO2− oxidation in maintaining the marine fixed N inventory.
Effectiveness of CMIP5 Decadal Experiments for Interannual Rainfall Prediction Over Australia
Authors: Choudhury Dipayan , Mehrotra Rajeshwar , Sharma Ashish , Sen Gupta Alexander , Sivakumar Bellie 
Published: August 2019

AbstractPhase five of the Coupled Model Intercomparison Project enabled a range of decadal modeling experiments where climate models were initialized with observations and allowed to evolve freely for 10–30 years. However, climate models struggle to realistically simulate rainfall and the skill of rainfall prediction in decadal experiments is poor. Here, we examine how predictions of sea surface temperature anomaly (SSTA) indices from Coupled Model Intercomparison Project Phase 5 decadal experiments can provide skillful rainfall forecasts at interannual timescales for Australia. Forecasts of commonly used SSTA indices relevant to Australian seasonal rainfall are derived from decadal hindcasts of six different climate models and corrected for model drift. The corrected indices are then combined to form a multimodel ensemble. The resultant forecasts are used as predictors in a statistical rainfall model developed in this study. As SSTA forecasts lose skill with increasing lead time, a new methodology for predicting interannual rainfall is proposed. We allow our statistical prediction model to evolve with lead time while accounting for the loss of skill in SSTA forecasts instead of using one statistical model for all lead times. Results in this pilot study across two of the largest climate zones in Australia show that SSTA outputs from the decadal experiments provide enhanced skill in rainfall prediction over using the conventional model (based purely on lagged observed indices) up to a maximum of three years ahead. This methodology could be used more broadly for other regions around the world where rainfall variability is known to have strong links to ocean temperatures.
Global‐Scale Observations of the Equatorial Ionization Anomaly
Authors: Eastes R. W. , Solomon S. C. , Daniell R. E. , Anderson D. N. , Burns A. G. , England S. L. , Martinis C. R. , McClintock W. E. 
Published: August 2019

AbstractThe National Aeronautics and Space Administration Global‐scale Observations of the Limb and Disk ultraviolet spectrograph has been imaging the equatorial ionization anomaly (EIA), regions of the ionosphere with enhanced electron density north and south of the magnetic equator, since October 2018. The initial 3 months of observations was during solar minimum conditions, and they included observations in December solstice of unanticipated variability and depleted regions. Depletions are seen on most nights, in contrast to expectations from previous space‐based observations. The variety of scales and morphologies also pose challenges to understanding of the EIA. Abrupt changes in the EIA location, which could be related to in situ measurements of large‐scale depletion regions, are observed on some nights. Such synoptic‐scale disruptions have not been previously identified.
Compton Scattering Effects on the Spectral and Temporal Properties of Terrestrial Gamma‐Ray Flashes
Authors: Xu Wei , Celestin Sebastien , Pasko Victor P. , Marshall Robert A. 
Published: August 2019

AbstractTerrestrial gamma‐ray flashes (TGFs) are high‐energy photon bursts originating from the Earth's atmosphere. In this study, using first‐principles Monte Carlo simulations, we quantify the effects of Compton scattering on the temporal and spectral properties of TGFs induced by a tilted source geometry. Modeling results indicate that the source orientation is a critical parameter in TGF analysis but has been significantly underestimated in previous studies. Offset distance between the lightning source and satellite location cannot be used as a single parameter characterizing Compton scattering effects. In the tilted geometry, Compton scattering effects are more pronounced in the falling part of TGF pulses and can lead to an increase of the falling part of TGF pulses by several tens of microseconds. Moreover, by performing curve‐fitting analysis on simulated TGF light curves, we explain how the symmetric and asymmetric pulses measured by the Gamma‐Ray Burst Monitor on Fermi satellite are consistent with the Compton scattering effects. Fermi‐measured TGF pulses can be fully explained using Gaussian‐distributed TGF sources with an average duration of ∼206 μs.
The Stability of the AMOC During Heinrich Events Is Not Dependent on the AMOC Strength in an Intermediate Complexity Earth System Model Ensemble
Authors: Goes Marlos , Murphy Lisa N. , Clement Amy C. 
Published: August 2019

AbstractPrevious studies that used Earth system models of intermediate complexity showed that stronger background winds drove a more vigorous and stable Atlantic Meridional Overturning Circulation (AMOC), while those with weaker winds had a more sluggish and unstable AMOC. In other studies, ensembles under vertical mixing uncertainty showed the opposite effect, where the simulations with a stronger AMOC were more unstable. To tackle this conundrum, we produce a model ensemble featuring uncertainties related to wind forcing and vertical mixing to understand the role of feedbacks on the AMOC stability. We show that the stability of the AMOC is not influenced by vertical mixing and the AMOC strength, and rather, it is determined by the strength of the Northern Hemisphere winds. Paleoproxies indicate an AMOC shutdown during the last Heinrich Stadial. Our comparisons to sea surface temperature proxies show a better fit with the simulations under a stable AMOC, which corresponds to a forced off‐state. The sign of the AMOC‐driven freshwater transport in the South Atlantic, which is regarded as an index for its stability, is shown not to be an absolute measure, although its evolution agrees with the salt advection feedback.
LncRNA NR_003923 promotes cell proliferation, migration, fibrosis, and autophagy via the miR-760/miR-215-3p/IL22RA1 axis in human Tenon’s capsule fibroblasts
Authors: Zhao Yang , Zhang Feng , Pan Zheng , Luo Haomin , Liu Ke , Duan Xuanchu 
Published: August 2019

AbstractNoncoding RNAs (ncRNAs), including long ncRNAs (lncRNA) have manifested an important role in the pathophysiology of many diseases. Glaucoma is a primary cause of irreversible blindness worldwide. However, the involvement of lncRNAs in glaucoma remains largely unknown. Here, we performed the lncRNA expression assay based on clinical tissues and identified a specific functional lncRNA, NR_003923, and investigated its potential role in glaucoma. Knockdown of NR_003923 in human Tenon’s capsule fibroblast cells (HTFs) inhibited TGF-β-induced cell migration, proliferation, fibrosis, and autophagy. The dual luciferase reporter assay confirmed that miR-760 and miR-215-3p interacted with NR_003923. miR-760 and miR-215-3p inhibitor reversed the effects of NR_003923 and TGF-β-induced cell apoptosis. Moreover, the expression of miR-760 and miR-215-3p was decreased in glaucoma comparing with control. Furthermore, through microarray we found IL22RA1 was increased in glaucoma and both of miR-760 and miR-215-3p bound to the 3′ UTR of IL22RA1. Overexpression of IL22RA1 enhanced HTFs migration and proliferation, while miR-760 and miR-215-3p mimics reversed these promotive biological roles induced by IL22RA1. In conclusion, NR_003923 and IL22RA1 might contribute to glaucoma progression and be a novel and potential biomarkers and therapeutic targets for glaucoma.
Morphogenesis of extra-embryonic tissues directs the remodelling of the mouse embryo at implantation
Authors: Christodoulou Neophytos , Weberling Antonia , Strathdee Douglas , Anderson Kurt I. , Timpson Paul , Zernicka-Goetz Magdalena 
Published: August 2019

AbstractMammalian embryos change shape dramatically upon implantation. The cellular and molecular mechanism underlying this transition are largely unknown. Here, we show that this transition is directed by cross talk between the embryonic epiblast and the first extra-embryonic tissue, the trophectoderm. Specifically, we show via visualisation of a Cdx2-GFP reporter line and pharmacologically mediated loss and gain of function experiments that the epiblast provides FGF signal that results in differential fate acquisition in the multipotent trophectoderm leading to the formation of a tissue boundary within this tissue. The trophectoderm boundary becomes essential for expansion of the tissue into a multi-layered epithelium. Folding of this multi-layered trophectoderm induces spreading of the second extra-embryonic tissue, the primitive endoderm. Together, these events remodel the pre-implantation embryo into its post-implantation cylindrical shape. Our findings uncover how communication between embryonic and extra-embryonic tissues provides positional cues to drive shape changes in mammalian development during implantation.
S100A9 extends lifespan in insulin deficiency
Authors: Ramadori Giorgio , Ljubicic Sanda , Ricci Serena , Mikropoulou Despoina , Brenachot Xavier , Veyrat-Durebex Christelle , Aras Ebru , Ioris Rafael M. , Altirriba Jordi , Malle Elisabeth , Foell Dirk , Vogl Thomas , Coppari Roberto 
Published: August 2019

AbstractTens of millions suffer from insulin deficiency (ID); a defect leading to severe metabolic imbalance and death. The only means for management of ID is insulin therapy; yet, this approach is sub-optimal and causes life-threatening hypoglycemia. Hence, ID represents a great medical and societal challenge. Here we report that S100A9, also known as Calgranulin B or Myeloid-Related Protein 14 (MRP14), is a leptin-induced circulating cue exerting beneficial anti-diabetic action. In murine models of ID, enhanced expression of S100A9 alone (i.e. without administered insulin and/or leptin) slightly improves hyperglycemia, and normalizes key metabolic defects (e.g. hyperketonemia, hypertriglyceridemia, and increased hepatic fatty acid oxidation; FAO), and extends lifespan by at least a factor of two. Mechanistically, we report that Toll-Like Receptor 4 (TLR4) is required, at least in part, for the metabolic-improving and pro-survival effects of S100A9. Thus, our data identify the S100A9/TLR4 axis as a putative target for ID care.
CD146-HIF-1α hypoxic reprogramming drives vascular remodeling and pulmonary arterial hypertension
Authors: Luo Yongting , Teng Xiao , Zhang Lingling , Chen Jianan , Liu Zheng , Chen Xuehui , Zhao Shuai , Yang Sai , Feng Jing , Yan Xiyun 
Published: August 2019

AbstractPulmonary arterial hypertension (PAH) is a vascular remodeling disease of cardiopulmonary units. No cure is currently available due to an incomplete understanding of vascular remodeling. Here we identify CD146-hypoxia-inducible transcription factor 1 alpha (HIF-1α) cross-regulation as a key determinant in vascular remodeling and PAH pathogenesis. CD146 is markedly upregulated in pulmonary artery smooth muscle cells (PASMCs/SMCs) and in proportion to disease severity. CD146 expression and HIF-1α transcriptional program reinforce each other to physiologically enable PASMCs to adopt a more synthetic phenotype. Disruption of CD146-HIF-1α cross-talk by genetic ablation of Cd146 in SMCs mitigates pulmonary vascular remodeling in chronic hypoxic mice. Strikingly, targeting of this axis with anti-CD146 antibodies alleviates established pulmonary hypertension (PH) and enhances cardiac function in two rodent models. This study provides mechanistic insights into hypoxic reprogramming that permits vascular remodeling, and thus provides proof of concept for anti-remodeling therapy for PAH through direct modulation of CD146-HIF-1α cross-regulation.
Theoretical analysis of spectral lineshapes from molecular dynamics
Authors: Cupo Andrew , Tristant Damien , Rego Kyle , Meunier Vincent 
Published: August 2019

AbstractConventional methods for calculating anharmonic phonon properties are computationally expensive. To address this issue, a theoretical approach was developed for the accelerated calculation of vibrational lineshapes for spectra obtained from finite-time molecular dynamics. The method gives access to the effect of anharmonicity-induced frequency shift and lifetime, as well as simulation broadening. For a toy model we demonstrate at least an order of magnitude reduction in the number of simulation steps needed to obtain converged vibrational properties in nearly all cases considered as compared to the standard extraction procedure. The theory is also illustrated for graphene, hexagonal boron nitride, and silicon at the density functional theory level, with up to nearly a factor of 9 reduction in the required simulation time to reach convergence in the vibrational frequencies and lifetimes. In general, we expect the newly developed method to outperform the standard procedure when the anharmonicity is sufficiently weak so that well-defined renormalized phonon quasiparticles emerge. Our extension of signal analysis to material vibrations represents a state-of-the-art advance in calculating temperature-dependent phonon properties and could be implemented in computational materials discovery packages that search for thermoelectric materials for instance, since the thermal conductivity contribution to ZT depends strongly on these characteristics.
Impaired Systolic and Diastolic Left Ventricular Function in Children with Chronic Kidney Disease - Results from the 4C Study
Authors: Doyon Anke , Haas Pascal , Erdem Sevcan , Ranchin Bruno , Kassai Behrouz , Mencarelli Francesca , Lugani Francesca , Harambat Jerome , Matteucci Maria Chiara , Chinali Marcello , Habbig Sandra , Zaloszyc Ariane , Testa Sara , Vidal Enrico , Gimpel Charlotte , Azukaitis Karolis , Kovacevic Alexander , Querfeld Uwe , Schaefer Franz 
Published: August 2019

AbstractChildren with chronic kidney disease suffer from excessive cardiovascular mortality and early alterations of the cardiovascular system. Tissue doppler imaging is a validated echocardiographic tool to assess early systolic and diastolic cardiac dysfunction. We hypothesized that tissue Doppler velocities would reveal reduced cardiac function in children with chronic kidney disease compared to healthy children. A standardized echocardiographic exam was performed in 128 patients of the Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C) Study aged 6–17 years with an estimated glomerular filtration rate (eGFR) below 60 ml/min/1.73 m2. Tissue Doppler measurements included early (E’) and late (A’) diastolic and systolic (S’) velocity at the mitral and septal annulus of the left ventricle. Measured values were normalized to z-scores using published reference data. Predictors of E’/A’, E/E’, S’ and left ventricular mass index (LVMI) were assessed by multiple linear regression analyses. Tissue Doppler E’ was reduced and tissue Doppler A’ increased, resulting in a reduced tissue Doppler E’/A’ ratio (z-score −0.14, p < 0.0001) indicating reduced diastolic function compared to healthy children. Reduced tissue Doppler E’/A’ Z-Scores were independently associated with lower eGFR (p = 0.002) and increased systolic blood pressure (p = 0.02). While E/E’ Z-Scores were increased (Z-score 0.57, p < 0.0001), patients treated with pharmacological RAS blockade but not with other antihypertensive treatments had significantly lower E/E’ and higher E’/A’ Z-Scores. Systolic tissue Doppler velocities were significantly decreased (Z-score −0.24, p = 0.001) and inversely correlated with E/E’ Z-Scores (r = −0.41, p < 0.0001). LVMI was not associated with systolic or diastolic tissue Doppler velocities. Concentric left ventricular hypertrophy showed a tendency to lower S’ in multivariate analysis (p = 0.13) but no association to diastolic function. Concentric left ventricular geometry was significantly associated with lower midwall fractional shortening. In summary, systolic and diastolic function assessed by tissue Doppler is impaired. eGFR, systolic blood pressure and the type of antihypertensive medications are significant predictors of diastolic function in children with CKD. Left ventricular morphology is largely independent of tissue Doppler velocities. Tissue Doppler velocities provide sensitive information about early left ventricular dysfunction in this population.
Electrical stimulation shifts healing/scarring towards regeneration in a rat limb amputation model
Authors: Oliveira K. M. C. , Barker J. H. , Berezikov E. , Pindur L. , Kynigopoulos S. , Eischen-Loges M. , Han Z. , Bhavsar M. B. , Henrich D. , Leppik L. 
Published: August 2019

AbstractDifferent species respond differently to severe injury, such as limb loss. In species that regenerate, limb loss is met with complete restoration of the limbs’ form and function, whereas in mammals the amputated limb’s stump heals and scars. In in vitro studies, electrical stimulation (EStim) has been shown to promote cell migration, and osteo- and chondrogenesis. In in vivo studies, after limb amputation, EStim causes significant new bone, cartilage and vessel growth. Here, in a rat model, the stumps of amputated rat limbs were exposed to EStim, and we measured extracellular matrix (ECM) deposition, macrophage distribution, cell proliferation and gene expression changes at early (3 and 7 days) and later stages (28 days). We found that EStim caused differences in ECM deposition, with less condensed collagen fibrils, and modified macrophage response by changing M1 to M2 macrophage ratio. The number of proliferating cells was increased in EStim treated stumps 7 days after amputation, and transcriptome data strongly supported our histological findings, with activated gene pathways known to play key roles in embryonic development and regeneration. In conclusion, our findings support the hypothesis that EStim shifts injury response from healing/scarring towards regeneration. A better understanding of if and how EStim controls these changes, could lead to strategies that replace scarring with regeneration.
Detection and targeting insulin growth factor receptor type 2 (IGF2R) in osteosarcoma PDX in mouse models and in canine osteosarcoma tumors
Authors: Karkare Sharayu , Allen Kevin J. H. , Jiao Rubin , Malo Mackenzie E. , Dawicki Wojciech , Helal Muath , Godson Dale L. , Dickinson Ryan , MacDonald-Dickinson Valerie , Yang Rui , Hoang Bang , Gorlick Richard , Geller David S. , Dadachova Ekaterina 
Published: August 2019

AbstractOsteosarcoma (OS) represents 3.4% of all childhood cancers with overall survival of 70% not improving in 30 years. The consistent surface overexpression of insulin-like growth factor-2 receptor (IGF2R) has been reported in commercial and patient-derived xenograft (PDX) OS cell lines. We aimed to assess efficacy and safety of treating PDX and commercial OS tumors in mice with radiolabeled antibody to IGF2R and to investigate IGF2R expression on canine OS tumors. IGF2R expression on human commercial lines 143B and SaOS2 and PDX lines OS-17, OS-33 and OS-31 was evaluated by FACS. The biodistribution and microSPECT/CT imaging with 111Indium-2G11 mAb was performed in 143B and OS-17 tumor-bearing SCID mice and followed by radioimmunotherapy (RIT) with 177Lutetium-2G11 and safety evaluation. IGF2R expression in randomly selected canine OS tumors was measured by immunohistochemistry. All OS cell lines expressed IGF2R. Biodistribution and microSPECT/CT revealed selective uptake of 2G11 mAb in 143B and OS-17 xenografts. RIT significantly slowed down the growth of OS-17 and 143B tumors without local and systemic toxicity. Canine OS tumors expressed IGF2R. This study demonstrates the feasibility of targeting IGF2R on OS in PDX and spontaneous canine tumors and sets the stage for further development of RIT of OS using comparative oncology.
Migration of Bacteriocins Across Gastrointestinal Epithelial and Vascular Endothelial Cells, as Determined Using In Vitro Simulations
Authors: Dreyer Leané , Smith Carine , Deane Shelly M. , Dicks Leon M. T. , van Staden Anton D. 
Published: August 2019

AbstractLittle is known about the migration of bacteriocins across human cells. In this study, we report on migration of three bacteriocins nisin, plantaricin 423 and bacST4SA across colonic adenocarcinoma (Caco-2) cells and human umbilical vein endothelial cells (HUVECs). Bacteriocins were fluorescently labelled while still maintaining antimicrobial activity. Migration of fluorescently labelled bacteriocins across monolayers was assessed in vitro using transmigration well inserts. After 3 h, 75% of nisin, 85% of plantaricin 423 and 82% of bacST4SA migrated across the Caco-2 cell monolayer. Over the same time span, 88% nisin, 93% plantaricin 423 and 91% bacST4SA migrated across the HUVEC monolayer. The viability of both cell types remained unchanged when exposed to 50 µM of nisin, plantaricin 423 or bacST4SA. The effect of human plasma on bacteriocin activity was also assessed. Activity loss was dependent on bacteriocin type and concentration, with the class-IIa bacteriocins retaining more activity compared to nisin. This is the first report of bacteriocins migrating across simulated gastrointestinal- and vascular-barriers. This study provides some of the first evidence that bacteriocins are capable of crossing the gut-blood-barrier. However, in vivo studies need to be performed to confirm these findings and expand on the role of bacteriocin migration across cell barriers.
Dispersal of allergenic pollen from Cryptomeria japonica and Chamaecyparis obtusa: characteristic annual fluctuation patterns caused by intermittent phase synchronisations
Authors: Ishibashi Akira , Sakai Kenshi 
Published: August 2019

AbstractTrees produce pollen during specific times of the year. Pollen can induce pollinosis, a type of allergic rhinitis, in humans. In Japan, allergenic pollen is mainly dispersed from February to May. Using data collected at 120 observation sites managed by the Japanese Ministry of the Environment, we studied the annual patterns of airborne allergenic pollen. The allergenic pollen showed an alternating ON–OFF cycle, but the length of the cycle differed among regions. We used an in-phase/out-of-phase analysis to quantify two characteristic features of the synchronisation. The degrees of phase synchronisation were strong in eastern and weak in western Japan. The pattern of allergenic pollen dispersal throughout Japan is typical intermittent synchronisation. This is the first study to evaluate allergenic pollen’s distribution from a phase synchronisation viewpoint.