bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between dietary intake of some antioxidant micronutrients with some inflammatory and antioxidant markers in active Rheumatoid Arthritis patients
Authors: Arablou Tahereh , Aryaeian Naheed , Djalali Mahmoud , Shahram Farhad , Rasouli Latifeh
Published: April 2019

Abstract. Background: Rheumatoid Arthritis (RA) is an autoimmune disease. Antioxidants intake and body antioxidants status are important in patients with RA. The aim of this study was to investigate the association between dietary intake of some antioxidant micronutrients with some inflammatory and antioxidant markers in patients with active rheumatoid arthritis and comparison with Recommended Dietary Allowance (RDA). Materials and Methods: In this cross-sectional study, eighty-seven patients with active rheumatoid arthritis were included. Dietary antioxidants intake was measured using 24-hour recall questionnaire and food record (3 days). Blood levels of inflammatory and antioxidant markers were determined by laboratory tests. The association between intake of antioxidants with inflammatory and antioxidant markers, and also with RDA were determined using Paired-Samples t-test and Pearson correlation by SPSS software. Results: The findings showed that intakes of vitamin E, zinc, and magnesium in patients were significantly lower and intakes of copper and selenium were significantly higher than RDA (P < 0.05). Significant negative correlations were observed between vitamin A intake with PGE2 [R = −0.31], vitamin C intake with IL-1β [R = −0.25], zinc intake with PGE2 [R = −0.30], IL-2 [R = −0.23], and the activity of glutathione reductase enzyme [R = −0.21], magnesium intake with PGE2 [R = −0.24], IL-1β [R = −0.23] and IL-2 [R = −0.25], and selenium intake with PGE2 [R = −0.21] (P < 0.05). Also, significant positive correlations were observed between intakes of vitamin E and copper with catalase enzyme activity [R = 0.22 and R = 0.21 respectively] (P < 0.05). Conclusion: Some of the antioxidant micronutrients play important roles in the reduction of inflammatory conditions and improve the function of antioxidant enzymes in patients with rheumatoid arthritis.
Visuell-statisches Arbeitsgedächtnistraining bei Vorschulkindern
Authors: Seitz-Stein Katja , Berner Valérie-D. , Lehner Susanne
Published: April 2019

Zusammenfassung. Mit der vorliegenden Arbeit werden die Fördermöglichkeit von visuell-räumlichen Arbeitsgedächtnisprozessen und mögliche Transfereffekte bei Vorschulkindern untersucht. In zwei Studien wurde eine identische visuell-statische Arbeitsgedächtnisaufgabe (Matrix) trainiert. Die Stichprobe umfasste für die erste Studie n = 22 Kinder und für die zweite Studie n = 33 Kinder. Die insgesamt N = 55 Vorschulkinder aus beiden Teilstudien trainierten zur Hälfte mit der Matrix-Aufgabe, die andere Hälfte der Kinder bildete die aktive Kontrollgruppe. Das visuell-statische Trainingsprogramm fand ebenso wie die Beschäftigung (Zeichnen zu erzählten Geschichten) in der Kontrollgruppe 9-mal in ca. 10- bis 15-minütigen Einzelsitzungen statt. Erfasst wurden mittels der AGTB ( Hasselhorn et al., 2012 ) die visuell-statische und die räumlich-dynamische Komponente des visuell-räumlichen Notizblocks sowie die phonologische Schleife und die zentrale Exekutive. Indikatoren für mathematische Basiskompetenzen wurden in Anlehnung an Krajewski (2014) erhoben. Neben dem Prä- und Posttest fand eine Follow-up-Erhebung nach ca. 10 Wochen statt. Unmittelbar nach dem Training deutete sich eine Zunahme der visuellen Arbeitsgedächtnisfunktionalität an, was im Follow-up zu großen Leistungsvorteilen der Trainingsgruppe gegenüber der Kontrollgruppe in der Matrixspanne führte ( d = 0.72). Proximaler Transfer auf die zweite Komponente des visuell-räumlichen Notizblocks konnte ebenso wenig gefunden werden wie Transfereffekte auf andere Arbeitsgedächtnisfunktionen. Auch distale Transfereffekte auf mathematische Vorläuferfertigkeiten blieben aus. Die Befunde werden vor dem Hintergrund basaler Trainingsansätze im Vorschulalter diskutiert.
A Three‐Way Balance in the Beaufort Gyre: The Ice‐Ocean Governor, Wind Stress, and Eddy Diffusivity
Authors: Doddridge Edward W. , Meneghello Gianluca , Marshall John , Scott Jeffery , Lique Camille
Published: April 2019

The Beaufort Gyre (BG) is a large anticyclonic circulation in the Arctic Ocean. Its strength is directly related to the halocline depth, and therefore also to the storage of freshwater. It has recently been proposed that the equilibrium state of the BG is set by the Ice‐Ocean Governor, a negative feedback between surface currents and ice‐ocean stress, rather than a balance between lateral mesoscale eddy fluxes and surface Ekman pumping. However, mesoscale eddies are present in the Arctic Ocean; it is therefore important to extend the Ice‐Ocean Governor theory to include lateral fluxes due to mesoscale eddies. Here, a nonlinear ordinary differential equation is derived that represents the effects of wind stress, the Ice‐Ocean Governor, and eddy fluxes. Equilibrium and time‐varying solutions to this three‐way balance equation are obtained and shown to closely match the output from a hierarchy of numerical simulations, indicating that the analytical model represents the processes controlling BG equilibration. The equilibration timescale derived from this three‐way balance is faster than the eddy equilibration timescale and slower than the Ice‐Ocean Governor equilibration timescales for most values of eddy diffusivity. The sensitivity of the BG equilibrium depth to changes in eddy diffusivity and the presence of the Ice‐Ocean Governor is also explored. These results show that predicting the response of the BG to changing surface forcing and sea ice conditions requires faithfully capturing the three‐way balance between the Ice‐Ocean Governor, wind stress, and eddy fluxes.
Hydrostatic Interfaces in Bodies With Nonhydrostatic Lithospheres
Authors: Wieczorek Mark A. , Beuthe Mikael , Rivoldini Attilio , Van Hoolst Tim
Published: April 2019

Below the lithospheres of the terrestrial planets, dwarf planets, and moons, density interfaces adjust over geologic time to align with surfaces of constant gravitational potential. It is well known that the shape of such hydrostatic surfaces is controlled by the pseudo‐rotational potential, tidal potential, and the induced potential of nonspherical density interfaces in the body. When a lithosphere is present, however, additional gravitational terms must be considered that arise from, for example, surface relief and crustal thickness variations. A first‐order formalism is presented for calculating the shape of hydrostatic density interfaces beneath the lithosphere when the gravity field and surface shape of the body are known. Using an arbitrary discretized density profile, the shapes are obtained by solving a simple matrix equation. As examples, lithospheric gravity anomalies account for about 10% of the relief along hydrostatic interfaces in Mars, whereas for the Moon, the lithospheric gravity is the dominant contributor to the core shape. Spherical harmonic degree‐1 mass anomalies in the lithosphere generate degree‐1 relief along the core‐mantle boundary, and for Mars and the Moon, the core is offset from the center of mass of the body by about 90 m. The moments of inertia of the core of these bodies are also misaligned with respect to the principal moments of the entire body. An improved crustal thickness map of Mars is constructed that accounts for gravity anomalies beneath the lithosphere, and the consequences of core relief on the Martian free core nutation are quantified.
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

In 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

The 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

Water 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

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 (>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

IRE1, 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

Iron 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.
Author Correction: Involvement of autophagy in hypoxia-BNIP3 signaling to promote epidermal keratinocyte migration
Authors: Zhang Junhui , Zhang Can , Jiang Xupin , Li Lingfei , Zhang Dongxia , Tang Di , Yan Tiantian , Zhang Qiong , Yuan Hongping , Jia Jiezhi , Hu Jiongyu , Zhang Jiaping , Huang Yuesheng
Published: April 2019

Following publication of the original article, it has come to our attention that the Materials and Methods section of the paper was missing. This is because this section was accidentally omitted from the final version of the manuscript when it was submitted to production. Both the PDF and HTML versions of the article have been updated with the missing section and references. As a result, the references at the end of article have been renumbered as well. We apologize for this inconvenience.
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

The 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

Insulin 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

Retinoid 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

Formaldehyde 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

Salience 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

Phenotypic 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

Endocrine 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

Retrospective 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

High-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.
Altered neural activity to monetary reward/loss processing in episodic migraine
Authors: Kocsel Natália , Galambos Attila , Szabó Edina , Édes Andrea Edit , Magyar Máté , Zsombók Terézia , Pap Dorottya , Kozák Lajos Rudolf , Bagdy György , Kökönyei Gyöngyi , Juhász Gabriella
Published: April 2019

The dysfunctions of the mesolimbic cortical reward circuit have been proposed to contribute to migraine pain. Although supporting empirical evidence was mainly found in connection with primary rewards or in chronic migraine where the pain experience is (almost) constant. Our goal however was to investigate the neural correlates of secondary reward/loss anticipation and consumption using the monetary incentive delay task in 29 episodic migraine patients and 41 headache-free controls. Migraine patients showed decreased activation in one cluster covering the right inferior frontal gyrus during reward consumption compared to controls. We also found significant negative correlation between the time of the last migraine attack before the scan and activation of the parahippocampal gyrus and the right hippocampus yielded to loss anticipation. During reward/loss consumption, a relative increase in the activity of the visual areas was observed the more time passed between the last attack and the scan session. Our results suggest intact reward/loss anticipation but altered reward consumption in migraine, indicating a decreased reactivity to monetary rewards. The findings also raise the possibility that neural responses to loss anticipation and reward/loss consumption could be altered by the proximity of the last migraine attack not just during pre-ictal periods, but interictally as well.
The Role of AMPARs in the Maturation and Integration of Caudal Ganglionic Eminence-Derived Interneurons into Developing Hippocampal Microcircuits
Authors: Akgül G. , Abebe D. , Yuan X. Q. , Auville K. , McBain C. J.
Published: April 2019

In the hippocampal CA1, caudal ganglionic eminence (CGE)-derived interneurons are recruited by activation of glutamatergic synapses comprising GluA2-containing calcium-impermeable AMPARs and exert inhibitory regulation of the local microcircuit. However, the role played by AMPARs in maturation of the developing circuit is unknown. We demonstrate that elimination of the GluA2 subunit (GluA2 KO) of AMPARs in CGE-derived interneurons, reduces spontaneous EPSC frequency coupled to a reduction in dendritic glutamatergic synapse density. Removal of GluA1&2&3 subunits (GluA1-3 KO) in CGE-derived interneurons, almost completely eliminated sEPSCs without further reducing synapse density, but increased dendritic branching. Moreover, in GluA1-3 KOs, the number of interneurons invading the hippocampus increased in the early postnatal period but converged with WT numbers later due to increased apoptosis. However, the CCK-containing subgroup increased in number, whereas the VIP-containing subgroup decreased. Both feedforward and feedback inhibitory input onto pyramidal neurons was decreased in GluA1-3 KO. These combined anatomical, synaptic and circuit alterations, were accompanied with a wide range of behavioural abnormalities in GluA1-3 KO mice compared to GluA2 KO and WT. Thus, AMPAR subunits differentially contribute to numerous aspects of the development and maturation of CGE-derived interneurons and hippocampal circuitry that are essential for normal behaviour.
Synthesis and characterization of polylactide/rice husk hydrochar composite
Authors: Nizamuddin Sabzoi , Jadhav Ankit , Qureshi Sundus Saeed , Baloch Humair Ahmed , Siddiqui M. T. H. , Mubarak N. M. , Griffin Gregory , Madapusi Srinivasan , Tanksale Akshat , Ahamed Mohd Imran
Published: April 2019

Polymer composites are fabricated by incorporating fillers into a polymer matrix. The intent for addition of fillers is to improve the physical, mechanical, chemical and rheological properties of the composite. This study reports on a unique polymer composite using hydrochar, synthesised by microwave-assisted hydrothermal carbonization of rice husk, as filler in polylactide matrix. The polylactide/hydrochar composites were fabricated by incorporating hydrochar in polylactide at 5%, 10%, 15% and 20 wt% by melt processing in a Haake rheomix at 170 °C. Both the neat polylactide and polylactide/hydrochar composite were characterized for mechanical, structural, thermal and rheological properties. The tensile modulus of polylactide/hydrochar composites was improved from 2.63 GPa (neat polylactide) to 3.16 GPa, 3.33 GPa, 3.54 GPa, and 4.24 GPa after blending with hydrochar at 5%, 10%, 15%, and 20%, respectively. Further, the incorporation of hydrochar had little effect on storage modulus (G′) and loss modulus (G″). The findings of this study reported that addition of hydrochar improves some characteristics of polylactide composites suggesting the potential of hydrochar as filler for polymer/hydrochar composites.
3D-QSAR, Docking, ADME/Tox studies on Flavone analogs reveal anticancer activity through Tankyrase inhibition
Authors: Alam Sarfaraz , Khan Feroz
Published: April 2019

Flavones are known as an inhibitor of tankyrase, a potential drug target of cancer. We here expedited the use of different computational approaches and presented a fast, easy, cost-effective and high throughput screening method to identify flavones analogs as potential tankyrase inhibitors. For this, we developed a field point based (3D-QSAR) quantitative structure-activity relationship model. The developed model showed acceptable predictive and descriptive capability as represented by standard statistical parameters r2 (0.89) and q2 (0.67). This model may help to explain SAR data and illustrated the key descriptors which were firmly related with the anticancer activity. Using the QSAR model a dataset of 8000 flavonoids were evaluated to classify the bioactivity, which resulted in the identification of 1480 compounds with the IC50 value of less than 5 µM. Further, these compounds were scrutinized through molecular docking and ADMET risk assessment. Total of 25 compounds identified which further analyzed for drug-likeness, oral bioavailability, synthetic accessibility, lead-likeness, and alerts for PAINS & Brenk. Besides, metabolites of screened compounds were also analyzed for pharmacokinetics compliance. Finally, compounds F2, F3, F8, F11, F13, F20, F21 and F25 with predicted activity (IC50) of 1.59, 1, 0.62, 0.79, 3.98, 0.79, 0.63 and 0.64, respectively were find as top hit leads. This study is offering the first example of a computationally-driven tool for prioritization and discovery of novel flavone scaffold for tankyrase receptor affinity with high therapeutic windows.
Formation of three-dimensional tubular endothelial cell networks under defined serum-free cell culture conditions in human collagen hydrogels
Authors: Andrée Birgit , Ichanti Houda , Kalies Stefan , Heisterkamp Alexander , Strauß Sarah , Vogt Peter-Maria , Haverich Axel , Hilfiker Andres
Published: April 2019

Implementation of tubular endothelial cell networks is a prerequisite for 3D tissue engineering of constructs with clinically relevant size as nourishment of cells is challenged by the diffusion limit. In vitro generation of 3D networks is often achieved under conditions using serum containing cell culture medium and/or animal derived matrices. Here, 3D endothelial cell networks were generated by using human umbilical vein endothelial cells (HUVECs) in combination with human adipose tissue derived stromal cells (hASCs) employing human collagen I as hydrogel and decellularized porcine small intestinal submucosa as starter matrix. Matrigel/rat tail collagen I hydrogel was used as control. Resulting constructs were cultivated either in serum-free medium or in endothelial growth medium-2 serving as control. Endothelial cell networks were quantified, tested for lumen formation, and interaction of HUVECs and hASCs. Tube diameter was slightly larger in constructs containing human collagen I compared to Matrigel/rat tail collagen I constructs under serum-free conditions. All other network parameters were mostly similar. Thereby, the feasibility of generating 3D endothelial cell networks under serum-free culture conditions in human collagen I as hydrogel was demonstrated. In summary, the presented achievements pave the way for the generation of clinical applicable constructs.
Temporal trends in normal weight central obesity and its associations with cardiometabolic risk among Chinese adults
Authors: Song Peige , Li Xue , Bu Yongjun , Ding Shibin , Zhai Desheng , Wang Erhui , Yu Zengli
Published: April 2019

Normal weight central obesity (NWCO), a distinct phenotype of obesity that is associated with a higher risk of cardiometabolic dysregulation, has received growing attention in the scientific literature. In this study, we aimed to report the prevalence of NWCO in the general Chinese adults and its secular trend from 1993 to 2011. The comorbid cardiometabolic risk of NWCO was also explored. Data from the China Health and Nutrition Survey (CHNS) 1993–2011 were obtained. NWCO was defined as the combination of a BMI of 18.5–23.9 kg/m2 and 1) a waist circumference (WC) of >85 cm in males or >80 cm in females (NWCO by WC); 2) a waist to height ratio (WHtR) of ≥0.5 (NWCO by WHtR); 3) a waist to hip ratio (WHR) of ≥0.9 in males or ≥0.85 in females (NWCO by WHR). We assessed the trend of NWCO prevalence with the generalized estimating equation method. The demographic, socioeconomic, geographic, behavioural and cardiometabolic predictors of NWCO were explored with multivariable logistic regression. From 1993 to 2011, the age-standardized prevalence of NWCO by WC increased from 6.65% (95% CI: 6.09–7.26) to 13.24% (95% CI: 12.58–13.93), and that of NWCO by WHtR and NWCO by WHR rose from 13.18% (95% CI: 12.41–13.98) to 17.06% (95% CI: 16.35–17.79) and from 16.14% (95% CI: 15.3–17.01) to 19.04% (95% CI: 18.25–19.85) respectively. The associated cardiometabolic factors of NWCO (by WC, WHtR and WHR) were hypertension, diabetes, insulin resistance, decreased insulin sensitivity, low high-density lipoprotein and elevated triglyceride. Moreover, NWCO by WC and NWCO by WHtR were associated with a decreased risk of impaired insulin secretion, and NWCO by WC was additionally linked to elevated total cholesterol. The prevalence of NWCO in the general Chinese adults increased significantly from 1993 to 2011. Effective strategies are needed to combat this epidemic and reduce its deleterious health outcomes.
Strong magnetoelectric coupling in mixed ferrimagnetic-multiferroic phases of a double perovskite
Authors: Kim M. K. , Moon J. Y. , Oh S. H. , Oh D. G. , Choi Y. J. , Lee N.
Published: April 2019

Exploring new magnetic materials is essential for finding advantageous functional properties such as magnetoresistance, magnetocaloric effect, spintronic functionality, and multiferroicity. Versatile classes of double perovskite compounds have been recently investigated because of intriguing physical properties arising from the proper combination of several magnetic ions. In this study, it is observed that the dominant ferrimagnetic phase is coexisted with a minor multiferroic phase in single-crystalline double-perovskite Er2CoMnO6. The majority portion of the ferrimagnetic order is activated by the long-range order of Er3+ moments below TEr = 10 K in addition to the ferromagnetic order of Co2+ and Mn4+ moments arising at TC = 67 K, characterized by compensated magnetization at TComp = 3.15 K. The inverted magnetic hysteresis loop observed below TComp can be described by an extended Stoner–Wohlfarth model. The additional multiferroic phase is identified by the ferroelectric polarization of ~0.9 μC/m2 at 2 K. The coexisting ferrimagnetic and multiferroic phases appear to be strongly correlated in that metamagnetic and ferroelectric transitions occur simultaneously. The results based on intricate magnetic correlations and phases in Er2CoMnO6 enrich fundamental and applied research on magnetic materials through the scope of distinct magnetic characteristics in double perovskites.
Metabolic disturbances in synovial fluid are involved in the onset of synovitis in heifers with acute ruminal acidosis
Authors: Alarcon Pablo , Hidalgo Alejandra I. , Manosalva Carolina , Cristi Raul , Teuber Stefanie , Hidalgo Maria A. , Burgos Rafael A.
Published: April 2019

Acute ruminal acidosis (ARA) is the result of increased intake of highly fermentable carbohydrates, which frequently occurs in dairy cattle and is associated with aseptic polysynovitis. To characterise the metabolic changes in the joints of animals with ARA, we performed an untargeted gas chromatography–mass spectrometry (GC-MS)-based metabolomic analysis of synovial fluid. Seven heifers were challenged with an intraruminal oligofructose overload (13 g/kg of body weight [BW]) dissolved in water. Synovial fluid samples were collected at 0, 9 and 24 h post-overload. Metabolome analysis revealed the presence of 67 metabolites. At 9 h post-overload, glyceric acid, cellobiose, fructose and lactic acid were all increased, whereas at 24 h, sorbitol, lactic acid and fructose levels were all increased >10-fold. At 24 h, citric acid and threonine levels were significantly reduced. We detected increased L- and D-lactate, and the presence of interleukin-6 (IL-6) in synovial fluid. Furthermore, using bovine fibroblast-like synoviocytes, we observed that D-lactate induces IL-6 synthesis. Our results suggest that ARA produces severe metabolomic changes in synovial fluid, including disturbances in starch and sucrose metabolism, and increased lactate levels. These changes were observed prior to the appearance of synovitis, suggesting a potential role in the onset of polysynovitis.
Design and fabrication of surface capped palladium nanoclusters for the subnanomolar sensing of glutathione
Authors: Aneesh Padamadathil K. , Govind Chinju , Nambiar Sindhu R.
Published: April 2019

In this work, a palladium atomic cluster modified glassy carbon electrode (PdAC/GCE) was developed by potentiodynamic electrodeposition in the presence of an anionic surfactant for the electrochemical detection of glutathione (GSH).
2D MXene nanosheets enable small-sulfur electrodes to be flexible for lithium–sulfur batteries
Authors: Zhao Qian , Zhu Qizhen , Miao Jiawei , Zhang Peng , Xu Bin
Published: April 2019

A flexible small-sulfur electrode with MXene as a conductive binder and flexible backbone is constructed combining good flexibility, stable cycling and good rate performance.
Aqueous dynamic covalent assembly of molecular ladders and grids bearing boronate ester rungs
Authors: Dunn Megan F. , Wei Tao , Zuckermann Ronald N. , Scott Timothy F.
Published: April 2019

Mimicking the self-assembly of nucleic acid sequences into double-stranded molecular ladders that incorporate hydrogen bond-based rungs, dynamic covalent interactions enable the fabrication of molecular ladder and grid structures with covalent bond-based rungs.
NMR studies of Li mobility in NASICON-type glass-ceramic ionic conductors with optimized microstructure
Authors: Vyalikh Anastasia , Schikora Marc , Seipel Kaspar P. , Weigler Max , Zschornak Matthias , Meutzner Falk , Münchgesang Wolfram , Nestler Tina , Vizgalov Viktor , Itkis Daniil , Privalov Alexei F. , Vogel Michael , Meyer Dirk C.
Published: April 2019

Increase in grain connectivity and Li content improves ionic conductivity in Y-modified LAGP glass-ceramics.
Bi vacancy formation in BiFeO3 epitaxial thin films under compressive (001)-strain from first principles
Authors: Xia Lu , Tybell Thomas , Selbach Sverre M.
Published: April 2019

Bi vacancy formation upon epitaxial (001)-strain in BiFeO3 was investigated by Density Functional Theory (DFT) calculations.
Pancreatic islet surface engineering with a starPEG-chondroitin sulfate nanocoating
Authors: Yang Jingyi , Jiang Shan , Guan Yong , Deng Juan , Lou Shaofeng , Feng Dandan , Kong Deling , Li Chen
Published: April 2019

Islet transplantation is one of the most promising therapeutic options that could restore euglycaemia in type 1 diabetic individuals.
H2O2-responsive nano-prodrug for podophyllotoxin delivery
Authors: Ou Kunyong , Kang Yang , Chen Long , Zhang Xinyu , Chen Xuewen , Zheng Yinghao , Wu Jun , Guan Shuyu
Published: April 2019

A novel H2O2-responsive prodrug, POD-PEG NPs, for controlled drug delivery and cancer therapy.
Wire like diplatinum, triplatinum, and tetraplatinum complexes featuring X[PtCCCCCCCC]mPtX segments; iterative syntheses and functionalization for measurements of single molecule properties
Authors: Zheng Qinglin , Schneider Jakob F. , Amini Hashem , Hampel Frank , Gladysz John A.
Published: April 2019

The title complexes are accessed from platinum chloride and Z(CC)2SiMe3 (Z = Me3Sn, H) building blocks via oxidative homocouplings and cross couplings.