bluuebunny/crossref_metadata_2025_split huggingface dataset:
HSP70 is a negative regulator of NLRP3 inflammasome activation
Authors: Martine Pierre , Chevriaux Angélique , Derangère Valentin , Apetoh Lionel , Garrido Carmen , Ghiringhelli François , Rébé Cédric 
Published: March 2019

AbstractThe NOD-leucine rich repeat and pyrin containing protein 3 (NLRP3) inflammasome is a multi-protein complex, aimed at producing IL-1β in response to danger signals which must be tightly regulated. Here we investigated the importance of the stress sensor, Heat Shock Protein 70 (HSP70) on NLRP3 inflammasome activation. HSP70 deficiency leads to the worsening of NLRP3-dependent peritonitis in mice. HSP70 deficiency also enhances caspase-1 activation and IL-1β production in murine Bone Marrow-Derived Macrophages (BMDMs) under NLRP3 activator treatment in vitro. This observation is associated with an increased number and size of Apoptosis associated Speck-like protein containing a CARD domain (ASC)/NLRP3 specks. Conversely, the overexpression of HSP70 in BMDMs decreases caspase-1 activation and IL-1β production under NLRP3 activator treatment. HSP70 interacts with NLRP3 and this interaction is lost upon NLRP3 inflammasome activation. Heat shock inhibits NLRP3 inflammasome activation in vitro and inhibits peritonitis in mice. Therefore this study provides evidence on the inhibitory role of HSP70 on NLRP3 inflammasome and open the possibility of treating inflammatory diseases via HSP70 induction and/or by hyperthermia.
Pervasive function and evidence for selection across standing genetic variation in S. cerevisiae
Authors: Jakobson Christopher M. , She Richard , Jarosz Daniel F. 
Published: March 2019

AbstractQuantitative genetics aims to map genotype to phenotype, often with the goal of understanding how organisms evolved. However, it remains unclear whether the genetic variants identified are exemplary of evolution. Here we analyzed progeny of two wild Saccharomyces cerevisiae isolates to identify 195 loci underlying complex metabolic traits, resolving 107 to single polymorphisms with diverse molecular mechanisms. More than 20% of causal variants exhibited patterns of emergence inconsistent with neutrality. Moreover, contrary to drift-centric expectation, variation in diverse wild yeast isolates broadly exhibited this property: over 30% of shared natural variants exhibited phylogenetic signatures suggesting that they are not neutral. This pattern is likely attributable to both homoplasy and balancing selection on ancestral polymorphism. Variants that emerged repeatedly were more likely to have done so in isolates from the same ecological niche. Our results underscore the power of super-resolution mapping of ecologically relevant traits in understanding adaptation and evolution.
Photoregulated fluxional fluorophores for live-cell super-resolution microscopy with no apparent photobleaching
Authors: Halabi Elias A. , Pinotsi Dorothea , Rivera-Fuentes Pablo 
Published: March 2019

AbstractPhotoswitchable molecules have multiple applications in the physical and life sciences because their properties can be modulated with light. Fluxional molecules, which undergo rapid degenerate rearrangements in the electronic ground state, also exhibit switching behavior. The stochastic nature of fluxional switching, however, has hampered its application in the development of functional molecules and materials. Here we combine photoswitching and fluxionality to develop a fluorophore that enables very long (>30 min) time-lapse single-molecule localization microscopy in living cells with minimal phototoxicity and no apparent photobleaching. These long time-lapse experiments allow us to track intracellular organelles with unprecedented spatiotemporal resolution, revealing new information of the three-dimensional compartmentalization of synaptic vesicle trafficking in live human neurons.
Benchmark decadal forecast skill for terrestrial water storage estimated by an elasticity framework
Authors: Zhu Enda , Yuan Xing , Wood Andrew W. 
Published: March 2019

AbstractA reliable decadal prediction of terrestrial water storage (TWS) is critical for a sustainable management of freshwater resources and infrastructures. However, the dependence of TWS forecast skill on the accuracy of initial hydrological conditions and decadal climate forecasts is not clear, and the baseline skill remains unknown. Here we use decadal climate hindcasts and perform hydrological ensemble simulations to estimate a benchmark decadal forecast skill for TWS over global major river basins with an elasticity framework that considers varying skill of initial conditions and climate forecasts. The initial condition skill elasticity is higher than climate forecast skill elasticity over many river basins at 1–4 years lead, suggesting the dominance of initial conditions at short leads. However, our benchmark skill for TWS is significantly higher than initial conditions-based forecast skill over 25 and 31% basins for the leads of 1–4 and 3–6 years, and incorporating climate prediction can significantly increase TWS prediction skill over half of the river basins at long leads, especially over mid- and high-latitudes. Our findings imply the possibility of improving decadal TWS forecasts by using dynamical climate prediction information, and the necessity of using the new benchmark skill for verifying the success of decadal hydrological forecasts.
Environmental degradation of high-temperature protective coatings for ceramic-matrix composites in gas-turbine engines
Authors: Padture Nitin P. 
Published: March 2019

AbstractThe need for higher efficiencies and performance in gas-turbine engines that propel aircraft in the air, and generate electricity on land, is pushing the operating temperatures of the engines to unprecedented levels. Replacing some of the current hot-section metallic components with ceramic-matrix composites (CMCs) is making that possible. A high-temperature ceramic coatings system, that includes environmental-barrier coatings (EBCs), are needed to protect CMCs. However, these coatings undergo degradation in the highly hostile environment of the gas-turbine engine consisting of a combination of high gas temperatures, pressures, and velocities. In addition, there is the ubiquitous presence of steam (a combustion by-product) and occasional ingestion of calcia-magnesia-aluminosilicates (CMASs) in the form of dust, sand, or ash from the environment. Steam can cause corrosion of EBCs, and the molten CMAS deposits can react with the EBCs resulting in their failure. This article provides a perspective on the understanding of these degradation mechanisms, and possible approaches, guided by that understanding, for mitigating the degradation. An outlook on the future challenges and opportunities is presented.
Improved Detection of Visual Field Progression Using a Spatiotemporal Boundary Detection Method
Authors: Berchuck Samuel I. , Mwanza Jean-Claude , Tanna Angelo P. , Budenz Donald L. , Warren Joshua L. 
Published: March 2019

AbstractGlaucoma is the leading cause of irreversible blindness worldwide and requires regular monitoring upon diagnosis to ascertain whether the disease is stable or progressing. However, making this determination remains a difficult clinical task. Recently, a novel spatiotemporal boundary detection predictor of glaucomatous visual field (VF) progression (STBound) was developed. In this work, we explore the ability of STBound to differentiate progressing and non-progressing glaucoma patients in comparison to existing methods. STBound, Spatial PROGgression, and traditional trend-based progression methods (global index (GI) regression, mean regression slope, point-wise linear regression, permutation of pointwise linear regression) were applied to longitudinal VF data from 191 eyes of 91 glaucoma patients. The ability of each method to identify progression was compared using Akaike information criterion (AIC), full/partial area under the receiver operating characteristic curve (AUC/pAUC), sensitivity, and specificity. STBound offered improved diagnostic ability (AIC: 197.77 vs. 204.11–217.55; AUC: 0.74 vs. 0.63–0.70) and showed no correlation (r: −0.01–0.11; p-values: 0.11–0.93) with the competing methods. STBound combined with GI (the top performing competitor) provided improved performance over all individual metrics and compared to all metrics combined with GI (all p-values < 0.05). STBound may be a valuable diagnostic tool and can be used in conjunction with existing methods.
Phase-pure VO2 nanoporous structure for binder-free supercapacitor performances
Authors: Basu Raktima , Ghosh Subrata , Bera Santanu , Das A. , Dhara S. 
Published: March 2019

AbstractVanadium oxides are anticipated as a high-performance energy storage electrode due to their coupled double layer and pseudo-capacitative charge storage mechanism. In the present work, we investigated the influence of different structural phases of as-grown VO2 nanoporous structure and corresponding oxidation states on the supercapacitor performance. This nanoporous structure facilitates fast ion diffusion and transport. It is shown that stoichiometric monoclinic VO2, with V oxidation state of +4, provides superior charge storage capacity with a capacitance value of 33 mF/cm2, capacitance retention of 93.7% and Coulombic efficiency of 98.2%, to those for VO2 structures with mixed oxidation states of V5+ and V4+. A comparable high energy density is also recorded for the sample with all V4+. Scanning Kelvin probe microscopy results clarify further the formation of space charge region between VO2 and carbon paper. These key findings indicate the potentiality of binder-free single phase monoclinic VO2 porous structure towards the next-generation micro-supercapacitor application.
DMSO induces drastic changes in human cellular processes and epigenetic landscape in vitro
Authors: Verheijen M. , Lienhard M. , Schrooders Y. , Clayton O. , Nudischer R. , Boerno S. , Timmermann B. , Selevsek N. , Schlapbach R. , Gmuender H. , Gotta S. , Geraedts J. , Herwig R. , Kleinjans J. , Caiment F. 
Published: March 2019

AbstractThough clinical trials for medical applications of dimethyl sulfoxide (DMSO) reported toxicity in the 1960s, later, the FDA classified DMSO in the safest solvent category. DMSO became widely used in many biomedical fields and biological effects were overlooked. Meanwhile, biomedical science has evolved towards sensitive high-throughput techniques and new research areas, including epigenomics and microRNAs. Considering its wide use, especially for cryopreservation and in vitro assays, we evaluated biological effect of DMSO using these technological innovations. We exposed 3D cardiac and hepatic microtissues to medium with or without 0.1% DMSO and analyzed the transcriptome, proteome and DNA methylation profiles. In both tissue types, transcriptome analysis detected >2000 differentially expressed genes affecting similar biological processes, thereby indicating consistent cross-organ actions of DMSO. Furthermore, microRNA analysis revealed large-scale deregulations of cardiac microRNAs and smaller, though still massive, effects in hepatic microtissues. Genome-wide methylation patterns also revealed tissue-specificity. While hepatic microtissues demonstrated non-significant changes, findings from cardiac microtissues suggested disruption of DNA methylation mechanisms leading to genome-wide changes. The extreme changes in microRNAs and alterations in the epigenetic landscape indicate that DMSO is not inert. Its use should be reconsidered, especially for cryopreservation of embryos and oocytes, since it may impact embryonic development.
SnoopLigase peptide-peptide conjugation enables modular vaccine assembly
Authors: Andersson Anne-Marie C. , Buldun Can M. , Pattinson David J. , Draper Simon J. , Howarth Mark 
Published: March 2019

AbstractFor many infectious diseases there is still no vaccine, even though potential protective antigens have been identified. Suitable platforms and conjugation routes are urgently needed to convert the promise of such antigens into broadly protective and scalable vaccines. Here we apply a newly established peptide-peptide ligation approach, SnoopLigase, for specific and irreversible coupling of antigens onto an oligomerization platform. SnoopLigase was engineered from a Streptococcus pneumoniae adhesin and enables isopeptide bond formation between two peptide tags: DogTag and SnoopTagJr. We expressed in bacteria DogTag linked to the self-assembling coiled-coil nanoparticle IMX313. This platform was stable over months at 37 °C when lyophilized, remaining reactive even after boiling. IMX-DogTag was efficiently coupled to two blood-stage malarial proteins (from PfEMP1 or CyRPA), with SnoopTagJr fused at the N- or C-terminus. We also showed SnoopLigase-mediated coupling of a telomerase peptide relevant to cancer immunotherapy. SnoopLigase-mediated nanoassembly enhanced the antibody response to both malaria antigens in a prime-boost model. Including or depleting SnoopLigase from the conjugate had little effect on the antibody response to the malarial antigens. SnoopLigase decoration represents a promising and accessible strategy for modular plug-and-display vaccine assembly, as well as providing opportunities for robust nanoconstruction in synthetic biology.
Optimization of Extraction Technology of Majun Mupakhi Ela and its Effect on Hydrocortisone-induced Kidney Yang Deficiency in Mice
Authors: Reheman Ayinuer , Gao Ze-yu , Tursun Xirali , Pu Xiao-Ping , Wu Tao , He Fei , Zhao Xin , Aisa Haji Akber 
Published: March 2019

AbstractWe used Box-Behnken design-based (BBD) response surface methodology (RSM) in this research to optimize the extraction process of Traditional medicine Majun Mupakhi Ela (MME) and evaluate its effect on hydrocortisone-induced kidney yang deficiency. Three independent parameters were applied to evaluate the maximum phosphodiesterase type 5 (PDE5) inhibition activity of MME extracts in vitro. The optimal processing conditions (extraction time 2 h, solid-liquid ratio 1:16, extraction once) gave a maximum PDE5 inhibition rate of 84.10%, flavonoid content of 0.49 mg/ml, icariin content of 0.028 mg/ml and targeted extraction yield of 26.50%. In animal experiments, MME extracts significantly increased the adrenal mass index, semen weight index, preputial gland weight index, and penis weight index in mice; in the middle and high dose group, the level of serum testosterone increased by 7664.29% and 14207.14% respectively, compared with the model group, and the level of PDE5 decreased by 67.22% and 74.69% respectively compared with the control group. These results indicate that MME has a significant positive effect on the hypothalamus-pituitary-gonadal axis, improve mating ability and not only has inhibits PDE5 activity but also significantly inhibits the expression of PDE5 in penile tissues, potential to become erectile dysfunction (ED) therapies for the clinical management of patients with kidney yang deficiency.
Genomewide Study of Epigenetic Biomarkers of Opioid Dependence in European- American Women
Authors: Montalvo-Ortiz Janitza L. , Cheng Zhongshan , Kranzler Henry R. , Zhang Huiping , Gelernter Joel 
Published: March 2019

AbstractThere is currently an epidemic of opioid use, overdose, and dependence in the United States. Although opioid dependence (OD) is more prevalent in men, opioid relapse and fatal opioid overdoses have recently increased at a higher rate among women. Epigenetic mechanisms have been implicated in the etiology of OD, though most studies to date have used candidate gene approaches. We conducted the first epigenome-wide association study (EWAS) of OD in a sample of 220 European-American (EA) women (140 OD cases, 80 opioid-exposed controls). DNA was derived from whole blood samples and EWAS was implemented using the Illumina Infinium HumanMethylationEPIC array. To identify differentially methylated CpG sites, we performed an association analysis adjusting for age, estimates of cell proportions, smoking status, and the first three principal components to correct for population stratification. After correction for multiple testing, association analysis identified three genome-wide significant differentially methylated CpG sites mapping to the PARG, RERE, and CFAP77 genes. These genes are involved in chromatin remodeling, DNA binding, cell survival, and cell projection. Previous genome-wide association studies have identified RERE risk variants in association with psychiatric disorders and educational attainment. DNA methylation age in the peripheral blood did not differ between OD subjects and opioid-exposed controls. Our findings implicate epigenetic mechanisms in OD and, if replicated, identify possible novel peripheral biomarkers of OD that could inform the prevention and treatment of the disorder.
Climate-Altered Wetlands Challenge Waterbird Use and Migratory Connectivity in Arid Landscapes
Authors: Haig Susan M. , Murphy Sean P. , Matthews John H. , Arismendi Ivan , Safeeq Mohammad 
Published: March 2019

AbstractWetlands in arid landscapes provide critical habitat for millions of migratory waterbirds across the world and throughout their annual cycle. The scope and scale of understanding avian use of these wetlands in conjunction with changes in climate are daunting yet critical to address lest we lose continent-wide migratory pathways. Here, we assess changes in waterbird use of North America’s Pacific Flyway in the Great Basin by examining water availability and climate trends over the past 100 years. We found recent (1980–2015) climate warming has significantly reduced the amount and shifted seasonality of water flowing into wetlands. Further, we found remarkable changes in waterbird species composition over time. We propose that a reduced hydroperiod and lower water quality from reduction in water level and flow limits sites used by waterbirds. These factors reduce chick survivorship as they cannot metabolize saline water, which makes suitable freshwater conditions a limiting resource. Collectively, climate-induced changes in Great Basin wetlands suggest a major shift in freshwater ecosystems, resulting in degradation of a continental migratory route. This work illustrates the importance of examining multi-scale changes in critical regional resources to understand their impact across a hemispheric flyway and provides a model to examine other flyways.
Bridging human chaperonopathies and microbial chaperonins
Authors: Conway de Macario Everly , Yohda Masafumi , Macario Alberto J. L. , Robb Frank T. 
Published: March 2019

AbstractChaperonins are molecular chaperones that play critical physiological roles, but they can be pathogenic. Malfunctional chaperonins cause chaperonopathies of great interest within various medical specialties. Although the clinical-genetic aspects of many chaperonopathies are known, the molecular mechanisms causing chaperonin failure and tissue lesions are poorly understood. Progress is necessary to improve treatment, and experimental models that mimic the human situation provide a promising solution. We present two models: one prokaryotic (the archaeonPyrococcus furiosus) with eukaryotic-like chaperonins and one eukaryotic (Chaetomium thermophilum), both convenient for isolation-study of chaperonins, and report illustrative results pertaining to a pathogenic mutation of CCT5.
The calcium channel subunit gamma-4 is regulated by MafA and necessary for pancreatic beta-cell specification
Authors: Luan Cheng , Ye Yingying , Singh Tania , Barghouth Mohammad , Eliasson Lena , Artner Isabella , Zhang Enming , Renström Erik 
Published: March 2019

AbstractVoltage-gated Ca2+ (CaV) channels trigger glucose-induced insulin secretion in pancreatic beta-cell and their dysfunction increases diabetes risk. These heteromeric complexes include the main subunit alpha1, and the accessory ones, including subunit gamma that remains unexplored. Here, we demonstrate that CaV gamma subunit 4 (CaVγ4) is downregulated in islets from human donors with diabetes, diabetic Goto-Kakizaki (GK) rats, as well as under conditions of gluco-/lipotoxic stress. Reduction of CaVγ4 expression results in decreased expression of L-type CaV1.2 and CaV1.3, thereby suppressing voltage-gated Ca2+ entry and glucose stimulated insulin exocytosis. The most important finding is that CaVγ4 expression is controlled by the transcription factor responsible for beta-cell specification, MafA, as verified by chromatin immunoprecipitation and experiments in beta-cell specific MafA knockout mice (MafAΔβcell). Taken together, these findings suggest that CaVγ4 is necessary for maintaining a functional differentiated beta-cell phenotype. Treatment aiming at restoring CaVγ4 may help to restore beta-cell function in diabetes.
High concentration of few‐layer graphene and MoS2 nanosheets using carboxyl methyl cellulose as a high‐performance stabiliser
Authors: Shang Jingqi , Ding Enyong , Xue Feng , Zeng Xingrong , Chen Jiewei , Xu Ning , Zhang Nianchun , Wei Qiushi 
Published: March 2019

This work report a facile, rapid and efficient approach to prepare high‐concentration graphene and MoS2 nanosheets through the liquid phase exfoliation of bulk materials with the method of high‐pressure homogenisation assisted by carboxyl methyl cellulose. The few‐layer graphene and MoS2 nanosheets dispersions are prepared under 100 MPa for 10 min at high concentrations up to 1.45 and 0.28 mg/ml. The two nanodispersions could be applied to prepare the polyvinyl alcohol composite with well dispersibility and thermal stability.
Plasma environment effects on K lines of astrophysical interest
Authors: Deprince J. , Bautista M. A. , Fritzsche S. , García J. A. , Kallman T. R. , Mendoza C. , Palmeri P. , Quinet P. 
Published: March 2019

Aims. In the context of black-hole accretion disks, the main goal of the present study is to estimate the plasma environment effects on the atomic structure and radiative parameters associated with the K-vacancy states in ions of the oxygen isonuclear sequence.
Methods. We used a time-averaged Debye–Hückel potential for both the electron–nucleus and the electron–electron interactions implemented in the fully relativistic multiconfiguration Dirac–Fock (MCDF) method.
Results. Modified ionization potentials, K thresholds, Auger widths, and radiative transition wavelengths and rates are reported for O I–O VII in plasma environments with electron temperature and density ranges 105−107 K and 1018−1022 cm−3.