bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recent Changes in the ISBA‐CTRIP Land Surface System for Use in the CNRM‐CM6 Climate Model and in Global Off‐Line Hydrological Applications
Authors: Decharme Bertrand , Delire Christine , Minvielle Marie , Colin Jeanne , Vergnes Jean‐Pierre , Alias Antoinette , Saint‐Martin David , Séférian Roland , Sénési Stéphane , Voldoire Aurore 
Published: April 2019

AbstractIn recent years, significant efforts have been made to upgrade physical processes in the ISBA‐CTRIP land surface system for use in fully coupled climate studies using the new CNRM‐CM6 climate model or in stand‐alone mode for global hydrological applications. Here we provide a thorough description of the new and improved processes implemented between the CMIP5 and CMIP6 versions of the model and evaluate the hydrology and thermal behavior of the model at the global scale. The soil scheme explicitly solves the one‐dimensional Fourier and Darcy laws throughout the soil, accounting for the dependency of hydraulic and thermal soil properties on soil organic carbon content. The snowpack is represented using a multilayer detailed internal‐process snow scheme. A two‐way dynamic flood scheme is added in which floodplains interact with the soil hydrology through reinfiltration of floodwater and with the overlying atmosphere through surface free‐water evaporation. Finally, groundwater processes are represented via a two‐dimensional diffusive unconfined aquifer scheme allowing upward capillarity rises into the superficial soil. This new system has been evaluated in off‐line mode using two different atmospheric forcings and against a large set of satellite estimates and in situ observations. While this study is not without weaknesses, its results show a real advance in modeling the physical aspects of the land surface with the new ISBA‐CTRIP version compared to the previous system. This increases our confidence that the model is able to represent the land surface physical processes accurately across the globe and in turn contribute to several important scientific and societal issues.
Quantifying the Impact of Uncertainty within the Longitudinal Dispersion Coefficient on Concentration Dynamics and Regulatory Compliance in Rivers
Authors: Camacho Suarez V. V. , Schellart A. N. A. , Brevis W. , Shucksmith J. D. 
Published: April 2019

AbstractThe one‐dimensional advection dispersion equation (1D ADE) is commonly used in practice to simulate pollutant transport processes for assessment and improvement of water quality conditions in rivers. Various studies have shown that the longitudinal dispersion coefficient used within the 1D ADE is influenced by a range of hydraulic and geomorphological conditions. This study aims to quantify the impact and importance of the parameter uncertainty associated with the longitudinal dispersion coefficient on modeled pollutant time‐concentration profiles and its implications for meeting compliance with water quality regulations. Six regression equations for estimating longitudinal dispersion coefficients are evaluated, and commonly used evaluation criteria were assessed for their suitability. A statistical evaluation of the regression equations based on their original calibration data sets resulted in percent bias (PBIAS) values between −47.01% and 20.78%. For a case study, uncertainty associated with the longitudinal dispersion coefficient was propagated to time‐concentration profiles using 1D ADE and Monte Carlo simulations, and 75% confidence interval bands of the pollutant concentration versus time profiles were derived. For two studied equations, the measured peak concentration values were above the simulated 87.5th percentile, and for the other four equations it was close to the 87.5th percentile. Subsequent uncertainty propagation analysis of four diverse rivers show the potential considerable impact on concentration‐duration‐frequency‐based water quality studies, with 1D ADE modeling producing predictions of quality standard compliance which varied over hundreds of kilometers.
Liquid and Vapor Water in Vadose Zone Profiles Above Deep Aquifers in Hyper‐Arid Environments
Authors: Assouline Shmuel , Kamai Tamir 
Published: April 2019

AbstractWater vapor is a key element of the water regime in unsaturated profiles above deep aquifers in hyper‐arid regions. However, the interactions between water phases and the resulting evaporation and condensation are poorly understood under such conditions. The main driver for vapor condensation in deep vadose zone profiles is the geothermal gradient, displaying a decrease in temperatures toward the soil surface, thereby promoting condensation. We have analyzed the water regime in deep unsaturated profiles, with and without the geothermal gradient, and considered two types of hydrological scenarios: (1) assuming hydraulic continuity of liquid water over the entire profile and (2) assuming the presence of an evaporative front in the profile above which water flows to the surface in the vapor phase. We considered homogeneous profiles of two soil types, investigating the distribution with depth of the different state variables: temperature, relative humidity, water potential, and vapor pressure and concentration. We found that during evaporation, only extreme conditions of high relative humidity near the surface could lead to condensation. In addition, even when hydraulic continuity of liquid water is assumed over the entire soil profile, potential condensation amounts are very small, practically negligible. For the case of a water table at 200‐m depth, condensation occurs only when the relative humidity at the surface is above 95% and is less than 1.5% of the amount of water in the vapor phase in the profile.
Affinity informs environmental cooperation between ammonia-oxidizing archaea (AOA) and anaerobic ammonia-oxidizing (Anammox) bacteria
Authors: Straka Levi L , Meinhardt Kelley A , Bollmann Annette , Stahl David A , Winkler Mari-K H 
Published: April 2019

Abstract
Anaerobic ammonia-oxidizing (Anammox) bacteria (AnAOB) rely on nitrite supplied by ammonia-oxidizing bacteria (AOB) and archaea (AOA). Affinities for ammonia and oxygen play a crucial role in AOA/AOB competition and their association with AnAOB. In this work we measured the affinity constants for ammonia and oxygen (half-saturation; km) of two freshwater AOA enrichments, an AOA soil isolate (N. viennensis), and a freshwater AnAOB enrichment. The AOA enrichments had similar kinetics (μmax ≈ 0.36 d−1, km,NH4 ≈ 0.78 µM, and km,O2 ≈ 2.9 µM), whereas N. viennensis had similar km values but lower μmax (0.23 d−1). In agreement with the current paradigm, these AOA strains showed a higher affinity for ammonia (lower km,NH4; 0.34–1.27 µM) than published AOB measurements (&gt;20 µM). The slower growing AnAOB (μmax ≈ 0.16 d−1) had much higher km values (km,NH4 ≈ 132 µM, km,NO2 ≈ 48 µM) and were inhibited by oxygen at low levels (half-oxygen inhibition; ki,O2 ≈ 0.092 µM). The higher affinity of AOA for ammonia relative to AnAOB, suggests AOA/AnAOB cooperation is only possible where AOA do not outcompete AnAOB for ammonia. Using a biofilm model, we show that environments of ammonia/oxygen counter diffusion, such as stratified lakes, favors this cooperation.
The unfolded protein response modulators GSK2606414 and KIRA6 are potent KIT inhibitors
Authors: Mahameed Mohamed , Wilhelm Thomas , Darawshi Odai , Obiedat Akram , Tommy Weiss-Sadan , Chintha Chetan , Schubert Thomas , Samali Afshin , Chevet Eric , Eriksson Leif A. , Huber Michael , Tirosh Boaz 
Published: April 2019

AbstractIRE1, PERK, and ATF6 are the three transducers of the mammalian canonical unfolded protein response (UPR). GSK2606414 is a potent inhibitor of PERK, while KIRA6 inhibits the kinase activity of IRE1. Both molecules are frequently used to probe the biological roles of the UPR in mammalian cells. In a direct binding assay, GSK2606414 bound to the cytoplasmic domain of KIT with dissociation constants (Kd) value of 664 ± 294 nM whereas KIRA6 showed a Kd value of 10.8 ± 2.9 µM. In silico docking studies confirmed a compact interaction of GSK2606414 and KIRA6 with KIT ATP binding pocket. In cultured cells, GSK2606414 inhibited KIT tyrosine kinase activity at nanomolar concentrations and in a PERK-independent manner. Moreover, in contrast to other KIT inhibitors, GSK2606414 enhanced KIT endocytosis and its lysosomal degradation. Although KIRA6 also inhibited KIT at nanomolar concentrations, it did not prompt KIT degradation, and rescued KIT from GSK2606414-mediated degradation. Consistent with KIT inhibition, nanomolar concentrations of GSK2606414 and KIRA6 were sufficient to induce cell death in a KIT signaling-dependent mast cell leukemia cell line. Our data show for the first time that KIT is a shared target for two seemingly unrelated UPR inhibitors at concentrations that overlap with PERK and IRE1 inhibition. Furthermore, these data underscore discrepancies between in vitro binding measurements of kinase inhibitors and inhibition of the tyrosine kinase receptors in living cells.
Iron-dependent CDK1 activity promotes lung carcinogenesis via activation of the GP130/STAT3 signaling pathway
Authors: Kuang Yanbin , Guo Wenzheng , Ling Jing , Xu Dongliang , Liao Yueling , Zhao Hui , Du Xiaohui , Wang Han , Xu Mingxin , Song Hongyong , Wang Tong , Jing Bo , Li Kaimi , Hu Min , Wu Wenjuan , Deng Jiong , Wang Qi 
Published: April 2019

AbstractIron dysregulation is associated with several diseases, including lung cancer, but the underlying mechanism is yet unknown. Iron directly binds CDK1, which is upregulated in several cancers, thereby promoting JAK1 phosphorylation and activation of STAT3 signaling to promote colorectal carcinogenesis. This study aimed to investigate the role of iron/CDK1/STAT3 signaling in lung carcinogenesis. We found that iron-dependent CDK1 activity upregulated IL-6 receptor subunit GP130 post-transcriptionally via phosphorylation of 4E-BP1, which is critical for activation of JAK/STAT3 signaling. CDK1 and STAT3 are essential for iron-mediated colony formation in lung cancer cell lines. CDK1 knockdown and iron chelator DFO decreased tumorigenicity and GP130/STAT3 signaling in vivo. Moreover, CDK1/GP130/STAT3 signaling were elevated in lung cancer tissues compared with adjacent normal lung tissues. Altogether, the present results suggest that CDK1 inhibition and iron deprivation are potential strategies to target GP130/STAT3 signaling to suppress lung cancer.
High-quality mesoporous graphene particles as high-energy and fast-charging anodes for lithium-ion batteries
Authors: Mo Runwei , Li Fan , Tan Xinyi , Xu Pengcheng , Tao Ran , Shen Gurong , Lu Xing , Liu Fang , Shen Li , Xu Bin , Xiao Qiangfeng , Wang Xiang , Wang Chongmin , Li Jinlai , Wang Ge , Lu Yunfeng 
Published: April 2019

AbstractThe application of graphene for electrochemical energy storage has received tremendous attention; however, challenges remain in synthesis and other aspects. Here we report the synthesis of high-quality, nitrogen-doped, mesoporous graphene particles through chemical vapor deposition with magnesium-oxide particles as the catalyst and template. Such particles possess excellent structural and electrochemical stability, electronic and ionic conductivity, enabling their use as high-performance anodes with high reversible capacity, outstanding rate performance (e.g., 1,138 mA h g−1at 0.2 C or 440 mA h g−1at 60 C with a mass loading of 1 mg cm−2), and excellent cycling stability (e.g., >99% capacity retention for 500 cycles at 2 C with a mass loading of 1 mg cm−2). Interestingly, thick electrodes could be fabricated with high areal capacity and current density (e.g., 6.1 mA h cm−2at 0.9 mA cm−2), providing an intriguing class of materials for lithium-ion batteries with high energy and power performance.
Mitotic regulators and the SHP2-MAPK pathway promote IR endocytosis and feedback regulation of insulin signaling
Authors: Choi Eunhee , Kikuchi Sotaro , Gao Haishan , Brodzik Karolina , Nassour Ibrahim , Yopp Adam , Singal Amit G. , Zhu Hao , Yu Hongtao 
Published: April 2019

AbstractInsulin controls glucose homeostasis and cell growth through bifurcated signaling pathways. Dysregulation of insulin signaling is linked to diabetes and cancer. The spindle checkpoint controls the fidelity of chromosome segregation during mitosis. Here, we show that insulin receptor substrate 1 and 2 (IRS1/2) cooperate with spindle checkpoint proteins to promote insulin receptor (IR) endocytosis through recruiting the clathrin adaptor complex AP2 to IR. A phosphorylation switch of IRS1/2 orchestrated by extracellular signal-regulated kinase 1 and 2 (ERK1/2) and Src homology phosphatase 2 (SHP2) ensures selective internalization of activated IR. SHP2 inhibition blocks this feedback regulation and growth-promoting IR signaling, prolongs insulin action on metabolism, and improves insulin sensitivity in mice. We propose that mitotic regulators and SHP2 promote feedback inhibition of IR, thereby limiting the duration of insulin signaling. Targeting this feedback inhibition can improve insulin sensitivity.
Oncogenic potential of truncated RXRα during colitis-associated colorectal tumorigenesis by promoting IL-6-STAT3 signaling
Authors: Ye Xiaohong , Wu Hua , Sheng Luoyan , Liu Yi-xin , Ye Fang , Wang Mo , Zhou Hu , Su Ying , Zhang Xiao-kun 
Published: April 2019

AbstractRetinoid X receptor-alpha (RXRα) is a potent regulator of inflammatory responses; however, its therapeutic potential for inflammatory cancer remains to be explored. We previously discovered that RXRα is abnormally cleaved in tumor cells and tissues, producing a truncated RXRα (tRXRα). Here, we show that transgenic expression of tRXRα in mice accelerates the development of colitis-associated colon cancer (CAC). The tumorigenic effect of tRXRα is primarily dependent on its expression in myeloid cells, which results in interleukin-6 (IL-6) induction and STAT3 activation. Mechanistic studies reveal an extensive interaction between tRXRα and TRAF6 in the cytoplasm of macrophages, leading to TRAF6 ubiquitination and subsequent activation of the NF-κB inflammatory pathway. K-80003, a tRXRα modulator derived from nonsteroidal anti-inflammatory drug (NSAID) sulindac, suppresses the growth of tRXRα-mediated colorectal tumor by inhibiting the NF-κB-IL-6-STAT3 signaling cascade. These results provide new insight into tRXRα action and identify a promising tRXRα ligand for treating CAC.
Critical role of formaldehyde during methanol conversion to hydrocarbons
Authors: Liu Yue , Kirchberger Felix M. , Müller Sebastian , Eder Moritz , Tonigold Markus , Sanchez-Sanchez Maricruz , Lercher Johannes A. 
Published: April 2019

AbstractFormaldehyde is an important intermediate product in the catalytic conversion of methanol to olefins (MTO). Here we show that formaldehyde is present during MTO with an average concentration of ~0.2 C% across the ZSM-5 catalyst bed up to a MeOH conversion of 70%. It condenses with acetic acid or methyl acetate, the carbonylation product of MeOH and DME, into unsaturated carboxylate or carboxylic acid, which decarboxylates into the first olefin. By tracing its reaction pathways of 13C-labeled formaldehyde, it is shown that formaldehyde reacts with alkenes via Prins reaction into dienes and finally to aromatics. Because its rate is one order of magnitude higher than that of hydrogen transfer between alkenes on ZSM-5, the Prins reaction is concluded to be the major reaction route from formaldehyde to produce dienes and aromatics. In consequence, formaldehyde increases the yield of ethene by enhancing the contribution of aromatic cycle.
Cortical recruitment determines learning dynamics and strategy
Authors: Ceballo Sebastian , Bourg Jacques , Kempf Alexandre , Piwkowska Zuzanna , Daret Aurélie , Pinson Pierre , Deneux Thomas , Rumpel Simon , Bathellier Brice 
Published: April 2019

AbstractSalience is a broad and widely used concept in neuroscience whose neuronal correlates, however, remain elusive. In behavioral conditioning, salience is used to explain various effects, such as stimulus overshadowing, and refers to how fast and strongly a stimulus can be associated with a conditioned event. Here, we identify sounds of equal intensity and perceptual detectability, which due to their spectro-temporal content recruit different levels of population activity in mouse auditory cortex. When using these sounds as cues in a Go/NoGo discrimination task, the degree of cortical recruitment matches the salience parameter of a reinforcement learning model used to analyze learning speed. We test an essential prediction of this model by training mice to discriminate light-sculpted optogenetic activity patterns in auditory cortex, and verify that cortical recruitment causally determines association or overshadowing of the stimulus components. This demonstrates that cortical recruitment underlies major aspects of stimulus salience during reinforcement learning.
Identification of human D lactate dehydrogenase deficiency
Authors: Monroe Glen R. , van Eerde Albertien M. , Tessadori Federico , Duran Karen J. , Savelberg Sanne M. C. , van Alfen Johanna C. , Terhal Paulien A. , van der Crabben Saskia N. , Lichtenbelt Klaske D. , Fuchs Sabine A. , Gerrits Johan , van Roosmalen Markus J. , van Gassen Koen L. , van Aalderen Mirjam , Koot Bart G. , Oostendorp Marlies , Duran Marinus , Visser Gepke , de Koning Tom J. , Calì Francesco , Bosco Paolo , Geleijns Karin , de Sain-van der Velden Monique G. M. , Knoers Nine V. , Bakkers Jeroen , Verhoeven-Duif Nanda M. , van Haaften Gijs , Jans Judith J. 
Published: April 2019

AbstractPhenotypic and biochemical categorization of humans with detrimental variants can provide valuable information on gene function. We illustrate this with the identification of two different homozygous variants resulting in enzymatic loss-of-function in LDHD, encoding lactate dehydrogenase D, in two unrelated patients with elevated D-lactate urinary excretion and plasma concentrations. We establish the role of LDHD by demonstrating that LDHD loss-of-function in zebrafish results in increased concentrations of D-lactate. D-lactate levels are rescued by wildtype LDHD but not by patients’ variant LDHD, confirming these variants’ loss-of-function effect. This work provides the first in vivo evidence that LDHD is responsible for human D-lactate metabolism. This broadens the differential diagnosis of D-lactic acidosis, an increasingly recognized complication of short bowel syndrome with unpredictable onset and severity. With the expanding incidence of intestinal resection for disease or obesity, the elucidation of this metabolic pathway may have relevance for those patients with D-lactic acidosis.
Early pregnancy exposure to endocrine disrupting chemical mixtures are associated with inflammatory changes in maternal and neonatal circulation
Authors: Kelley Angela S. , Banker Margaret , Goodrich Jaclyn M. , Dolinoy Dana C. , Burant Charles , Domino Steven E. , Smith Yolanda R. , Song Peter X. K. , Padmanabhan Vasantha 
Published: April 2019

AbstractEndocrine disrupting chemicals (EDCs) are ubiquitous, and pregnancy is a sensitive window for toxicant exposure. EDCs may disrupt the maternal immune system, which may lead to poor pregnancy outcomes. Most studies investigate single EDCs, even though “real life” exposures do not occur in isolation. We tested the hypothesis that uniquely weighted mixtures of early pregnancy exposures are associated with distinct changes in the maternal and neonatal inflammasome. First trimester urine samples were tested for 12 phthalates, 12 phenols, and 17 metals in 56 women. Twelve cytokines were measured in first trimester and term maternal plasma, and in cord blood after delivery. Spearman correlations and linear regression were used to relate individual exposures with inflammatory cytokines. Linear regression was used to relate cytokine levels with gestational age and birth weight. Principal component analysis was used to assess the effect of weighted EDC mixtures on maternal and neonatal inflammation. Our results demonstrated that maternal and cord blood cytokines were differentially associated with (1) individual EDCs and (2) EDC mixtures. Several individual cytokines were positively associated with gestational age and birth weight. These observed associations between EDC mixtures and the pregnancy inflammasome may have clinical and public health implications for women of childbearing age.
Bloodstream infections in patients living with HIV in the modern cART era
Authors: Taramasso L. , Liggieri F. , Cenderello G. , Bovis F. , Giannini B. , Mesini A. , Giacomini M. , Cassola G. , Viscoli C. , Di Biagio A. 
Published: April 2019

AbstractRetrospective multicentre study aiming at analysing the etiology, characteristics and outcome of bloodstream infections (BSI) in people living with HIV (PLWHIV) in an era of modern antiretroviral therapy. Between 2008 and 2015, 79 PLWHIV had at least 1 BSI, for a total of 119 pathogens isolated. Patients were mainly male (72.1%), previous intravenous drug users (55.7%), co-infected with HCV or HBV (58.2%) and in CDC stage C (60.8%). Gram-positive (G+) pathogens caused 44.5% of BSI, followed by Gram-negative (G−), 40.3%, fungi, 10.9%, and mycobacteria, 4.2%. Candida spp. and coagulase-negative staphylococci were the most frequent pathogens found in nosocomial BSI (17% each), while E.coli was prevalent in community-acquired BSI (25%). At the last available follow-up, (mean 3.2 ± 2.7 years) the overall crude mortality was 40.5%. Factors associated with mortality in the final multivariate analysis were older age, (p = 0.02; HR 3.8, 95%CI 1.2–11.7) CDC stage C (p = 0.02; HR 3.3, 95%CI 1.2–9.1), malignancies, (p = 0.004; HR 3.2, 95%CI 1.4–7.0) and end stage liver disease (p = 0.006; HR 3.4, 95%CI 1.4–8.0). In conclusion, the study found high mortality following BSI in PLWHIV. Older age, neoplastic comorbidities, end stage liver disease and advanced HIV stage were the main factors correlated to mortality.
Illumina sequencing of clinical samples for virus detection in a public health laboratory
Authors: Huang Bixing , Jennison Amy , Whiley David , McMahon Jamie , Hewitson Glen , Graham Rikki , De Jong Amanda , Warrilow David 
Published: April 2019

AbstractHigh-throughput sequencing (HTS) provides the opportunity, once a diagnostic result is obtained, to extract additional information from a virus-containing sample. Hence, it offers advantages over established quantitative amplification technology, such as quantitative PCR, particularly in a public health environment. At this early stage of its clinical application, there have been limited studies comparing HTS performance to that of the more established quantitative PCR technology for direct detection of viruses. In this pilot-scale study, we tested HTS with a range of viruses and sample types routinely encountered in a public health virology laboratory. In comparison with quantitative PCR, our HTS method was able to sensitively (92%) detect all viruses in any sample type with the exception of certain tissues. Moreover, sufficient nucleotide sequence information was obtained to enable genotyping of strains detected, thus providing additional useful epidemiological information. While HTS sensitivity may not yet match that of PCR, the added value through enhanced epidemiological data has considerable potential to enable real-time surveillance of circulating strains so as to facilitate rapid and appropriate response to outbreaks and virus zoonotic spillover events.