bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of an anti-fetal AChR monoclonal antibody isolated from a myasthenia gravis patient
Authors: Saxena Abhishek , Stevens Jo , Cetin Hakan , Koneczny Inga , Webster Richard , Lazaridis Konstantinos , Tzartos Socrates , Vrolix Kathleen , Nogales-Gadea Gisela , Machiels Barbie , Molenaar Peter C. , Damoiseaux Jan , De Baets Marc H. , Simon-Keller Katja , Marx Alexander , Vincent Angela , Losen Mario , Martinez-Martinez Pilar 
Published: October 2017

AbstractWe report here the sequence and functional characterization of a recombinantly expressed autoantibody (mAb 131) previously isolated from a myasthenia gravis patient by immortalization of thymic B cells using Epstein-Barr virus and TLR9 activation. The antibody is characterized by a high degree of somatic mutations as well as a 6 amino acid insertion within the VHCDR2. The recombinant mAb 131 is specific for the γ-subunit of the fetal AChR to which it bound with sub-nanomolar apparent affinity, and detected the presence of fetal AChR on a number of rhabdomyosarcoma cell lines. Mab 131 blocked one of the two α-bungarotoxin binding sites on the fetal AChR, and partially blocked the binding of an antibody (mAb 637) to the α-subunit of the AChR, suggesting that both antibodies bind at or near one ACh binding site at the α/γ subunit interface. However, mAb 131 did not reduce fetal AChR ion channel currents in electrophysiological experiments. These results indicate that mAb 131, although generated from an MG patient, is unlikely to be pathogenic and may make it a potentially useful reagent for studies of myasthenia gravis, rhabdomyosarcoma and arthrogryposis multiplex congenita which can be caused by fetal-specific AChR-blocking autoantibodies.
Indian Ocean corals reveal crucial role of World War II bias for twentieth century warming estimates
Authors: Pfeiffer M. , Zinke J. , Dullo W.-C. , Garbe-Schönberg D. , Latif M. , Weber M. E. 
Published: October 2017

AbstractThe western Indian Ocean has been warming faster than any other tropical ocean during the 20th century, and is the largest contributor to the global mean sea surface temperature (SST) rise. However, the temporal pattern of Indian Ocean warming is poorly constrained and depends on the historical SST product. As all SST products are derived from the International Comprehensive Ocean-Atmosphere dataset (ICOADS), it is challenging to evaluate which product is superior. Here, we present a new, independent SST reconstruction from a set of Porites coral geochemical records from the western Indian Ocean. Our coral reconstruction shows that the World War II bias in the historical sea surface temperature record is the main reason for the differences between the SST products, and affects western Indian Ocean and global mean temperature trends. The 20th century Indian Ocean warming pattern portrayed by the corals is consistent with the SST product from the Hadley Centre (HadSST3), and suggests that the latter should be used in climate studies that include Indian Ocean SSTs. Our data shows that multi-core coral temperature reconstructions help to evaluate the SST products. Proxy records can provide estimates of 20th century SST that are truly independent from the ICOADS data base.
Chromatin interaction networks revealed unique connectivity patterns of broad H3K4me3 domains and super enhancers in 3D chromatin
Authors: Thibodeau Asa , Márquez Eladio J. , Shin Dong-Guk , Vera-Licona Paola , Ucar Duygu 
Published: October 2017

AbstractBroad domain promoters and super enhancers are regulatory elements that govern cell-specific functions and harbor disease-associated sequence variants. These elements are characterized by distinct epigenomic profiles, such as expanded deposition of histone marks H3K27ac for super enhancers and H3K4me3 for broad domains, however little is known about how they interact with each other and the rest of the genome in three-dimensional chromatin space. Using network theory methods, we studied chromatin interactions between broad domains and super enhancers in three ENCODE cell lines (K562, MCF7, GM12878) obtained via ChIA-PET, Hi-C, and Hi-CHIP assays. In these networks, broad domains and super enhancers interact more frequently with each other compared to their typical counterparts. Network measures and graphlets revealed distinct connectivity patterns associated with these regulatory elements that are robust across cell types and alternative assays. Machine learning models showed that these connectivity patterns could effectively discriminate broad domains from typical promoters and super enhancers from typical enhancers. Finally, targets of broad domains in these networks were enriched in disease-causing SNPs of cognate cell types. Taken together these results suggest a robust and unique organization of the chromatin around broad domains and super enhancers: loci critical for pathologies and cell-specific functions.
Enzalutamide inhibits testosterone-induced growth of human prostate cancer xenografts in zebrafish and can induce bradycardia
Authors: Melong Nicole , Steele Shelby , MacDonald Morgan , Holly Alice , Collins Colin C. , Zoubeidi Amina , Berman Jason N. , Dellaire Graham 
Published: October 2017

AbstractThe zebrafish has become a popular human tumour xenograft model, particularly for solid tumours including prostate cancer (PCa). To date PCa xenotransplantation studies in zebrafish have not been performed in the presence of testosterone, even when employing androgen-dependent cell models, such as the LNCaP cell line. Thus, with the goal of more faithfully modelling the hormonal milieu in which PCa develops in humans, we sought to determine the effects of exogenous testosterone on the growth of LNCaP, or androgen-independent C4-2 cells xenografted into zebrafish embryos. Testosterone significantly increased engrafted LNCaP proliferation compared to control xenografts, which could be inhibited by co-administration of the anti-androgen receptor drug, enzalutamide. By contrast, C4-2 cell growth was not affected by either testosterone or enzalutamide. Enzalutamide also induced bradycardia and death in zebrafish embryos in a dose-dependent manner and strongly synergized with the potassium-channel blocking agent, terfenadine, known to induce long QT syndrome and cardiac arrhythmia. Together, these data not only indicate that testosterone administration should be considered in all PCa xenograft studies in zebrafish but also highlights the unique opportunity of this preclinical platform to simultaneously evaluate efficacy and toxicity of novel therapies and/or protective agents towards developing safer and more effective PCa treatments.
Gravel bars are sites of increased CO2 outgassing in stream corridors
Authors: Boodoo Kyle S. , Trauth Nico , Schmidt Christian , Schelker Jakob , Battin Tom J. 
Published: October 2017

AbstractStreams are significant sources of CO2to the atmosphere. Estimates of CO2evasion fluxes (fCO2) from streams typically relate to the free flowing water but exclude geomorphological structures within the stream corridor. We found that gravel bars (GBs) are important sources of CO2to the atmosphere, with on average more than twice as highfCO2as those from the streamwater, affectingfCO2at the level of entire headwater networks. Vertical temperature gradients resulting from the interplay between advective heat transfer and mixing with groundwater within GBs explained the observed variation infCO2from the GBs reasonably well. We propose that increased temperatures and their gradients within GBs exposed to solar radiation stimulate heterotrophic metabolism therein and facilitate the venting of CO2from external sources (e.g. downwelling streamwater, groundwater) within GBs. Our study shows that GBfCO2increasedfCO2from stream corridors by [median, (95% confidence interval)] 16.69%, (15.85–18.49%); 30.44%, (30.40–34.68%) and 2.92%, (2.90–3.0%), for 3rd, 4thand 5thorder streams, respectively. These findings shed new light on regional estimates offCO2from streams, and are relevant given that streamwater thermal regimes change owing to global warming and human alteration of stream corridors.
Surface reactivity of amphibole asbestos: a comparison between crocidolite and tremolite
Authors: Andreozzi Giovanni B. , Pacella Alessandro , Corazzari Ingrid , Tomatis Maura , Turci Francesco 
Published: October 2017

AbstractAmong asbestos minerals, fibrous riebeckite (crocidolite) and tremolite share the amphibole structure but largely differ in terms of their iron content and oxidation state. In asbestos toxicology, iron-generated free radicals are largely held as one of the causes of asbestos malignant effect. With the aim of clarifying i) the relationship between Fe occurrence and asbestos surface reactivity, and ii) how free-radical generation is modulated by surface modifications of the minerals, UICC crocidolite and fibrous tremolite from Maryland were leached from 1 day to 1 month in an oxidative medium buffered at pH 7.4 to induce redox alterations and surface rearrangements that may occur in body fluids. Structural and chemical modifications and free radical generation were monitored by HR-TEM/EDS and spin trapping/EPR spectroscopy, respectively. Free radical yield resulted to be dependent on few specific Fe2+ and Fe3+ surface sites rather than total Fe content. The evolution of reactivity with time highlighted that low-coordinated Fe ions primarily contribute to the overall reactivity of the fibre. Current findings contribute to explain the causes of the severe asbestos-induced oxidative stress at molecular level also for iron-poor amphiboles, and demonstrate that asbestos have a sustained surface radical activity even when highly altered by oxidative leaching.
Entropy production selects nonequilibrium states in multistable systems
Authors: Endres Robert G. 
Published: October 2017

AbstractFar-from-equilibrium thermodynamics underpins the emergence of life, but how has been a long-outstanding puzzle. Best candidate theories based on the maximum entropy production principle could not be unequivocally proven, in part due to complicated physics, unintuitive stochastic thermodynamics, and the existence of alternative theories such as the minimum entropy production principle. Here, we use a simple, analytically solvable, one-dimensional bistable chemical system to demonstrate the validity of the maximum entropy production principle. To generalize to multistable stochastic system, we use the stochastic least-action principle to derive the entropy production and its role in the stability of nonequilibrium steady states. This shows that in a multistable system, all else being equal, the steady state with the highest entropy production is favored, with a number of implications for the evolution of biological, physical, and geological systems.
Language and music phrase boundary processing in Autism Spectrum Disorder: An ERP study
Authors: DePriest John , Glushko Anastasia , Steinhauer Karsten , Koelsch Stefan 
Published: October 2017

AbstractAutism spectrum disorder (ASD) is frequently associated with communicative impairment, regardless of intelligence level or mental age. Impairment of prosodic processing in particular is a common feature of ASD. Despite extensive overlap in neural resources involved in prosody and music processing, music perception seems to be spared in this population. The present study is the first to investigate prosodic phrasing in ASD in both language and music, combining event-related brain potential (ERP) and behavioral methods. We tested phrase boundary processing in language and music in neuro-typical adults and high-functioning individuals with ASD. We targeted an ERP response associated with phrase boundary processing in both language and music – i.e., the Closure Positive Shift (CPS). While a language-CPS was observed in the neuro-typical group, for ASD participants a smaller response failed to reach statistical significance. In music, we found a boundary-onset music-CPS for both groups during pauses between musical phrases. Our results support the view of preserved processing of musical cues in ASD individuals, with a corresponding prosodic impairment. This suggests that, despite the existence of a domain-general processing mechanism (the CPS), key differences in the integration of features of language and music may lead to the prosodic impairment in ASD.
Transition state-based ST6Gal I inhibitors: Mimicking the phosphodiester linkage with a triazole or carbamate through an enthalpy-entropy compensation
Authors: Montgomery Andrew P. , Skropeta Danielle , Yu Haibo 
Published: October 2017

AbstractHuman β-galactoside α-2,6-sialyltransferase I (ST6Gal I) catalyses the synthesis of sialylated glycoconjugates. Overexpression of ST6Gal I is observed in many cancers, where it promotes metastasis through altered cell surface sialylation. A wide range of sialyltransferase inhibitors have been developed, with analogues structurally similar to the transition state exhibiting the highest inhibitory activity. To improve synthetic accessibility and pharmacokinetics of previously reported inhibitors, the replacement of the charged phosphodiester linker with a potential neutral isostere such as a carbamate or a 1,2,3-triazole has been investigated. Extensive molecular dynamics simulations have demonstrated that compounds with the alternate linkers could maintain key interactions with the human ST6Gal I active site, demonstrating the potential of a carbamate or a 1,2,3-triazole as a phosphodiester isostere. Free energy perturbation calculations provided energetic evidence suggesting that the carbamate and 1,2,3-triazole were slightly more favourable than the phosphodiester. Further exploration with free energy component, quasi-harmonic and cluster analysis suggested that there is an enthalpy-entropy compensation accounting for the replacement of the flexible charged phosphodiester with a neutral and rigid isostere. Overall, these simulations provide a strong rationale for the use of a carbamate or 1,2,3-triazole as a phosphodiester isostere in the development of novel inhibitors of human ST6Gal I.
Heparin at physiological concentration can enhance PEG-free in vitro infection with human hepatitis B virus
Authors: Choijilsuren Gansukh , Jhou Ren-Shiang , Chou Shu-Fan , Chang Ching-Jen , Yang Hwai-I , Chen Yang-Yuan , Chuang Wan-Long , Yu Ming-Lung , Shih Chiaho 
Published: October 2017

AbstractHepatitis B virus (HBV) is a blood-borne pathogen responsible for chronic hepatitis, cirrhosis, and liver cancer. The mechanism of HBV entry into hepatocytes remains to be investigated. Recently, sodium taurocholate cotransporting polypeptide (NTCP) was discovered as a major HBV receptor based on an in vitro infection system using NTCP-reconstituted HepG2 cells. However, this infection system relies on the compound polyethylene glycol (4% PEG), which is not physiologically relevant to human infection. High concentration of heparin has been commonly used as an inhibitor control for in vitro infection in the field. Surprisingly, we found that heparin at physiological concentration can enhance HBV infection in a PreS1-peptide sensitive, NTCP-dependent manner in both HepaRG and HepG2-NTCP-AS cells. O-sulfation of heparin is more important for the infection enhancement than N-sulfation. This system based on the HepG2-NTCP-AS cells can support in vitro infection with HBV genotypes B and C, as well as using serum samples from HBeAg positive and negative chronic carriers. In summary, our study provides a PEG-free infection system closely resembling human natural infection. In addition, it points to a future research direction for heparin and heparin-binding host factor(s) in the blood, which are potentially involved in viral entry. To our knowledge, this is the first soluble and circulatory host factor which can enhance HBV in vitro infection.
Graph theory reveals amygdala modules consistent with its anatomical subdivisions
Authors: Caparelli Elisabeth C. , Ross Thomas J. , Gu Hong , Liang Xia , Stein Elliot A. , Yang Yihong 
Published: October 2017

AbstractSimilarities on the cellular and neurochemical composition of the amygdaloid subnuclei suggests their clustering into subunits that exhibit unique functional organization. The topological principle of community structure has been used to identify functional subnetworks in neuroimaging data that reflect the brain effective organization. Here we used modularity to investigate the organization of the amygdala using resting state functional magnetic resonance imaging (rsfMRI) data. Our goal was to determine whether such topological organization would reliably reflect the known neurobiology of individual amygdaloid nuclei, allowing for human imaging studies to accurately reflect the underlying neurobiology. Modularity analysis identified amygdaloid elements consistent with the main anatomical subdivisions of the amygdala that embody distinct functional and structural properties. Additionally, functional connectivity pathways of these subunits and their correlation with task-induced amygdala activation revealed distinct functional profiles consistent with the neurobiology of the amygdala nuclei. These modularity findings corroborate the structure–function relationship between amygdala anatomical substructures, supporting the use of network analysis techniques to generate biologically meaningful partitions of brain structures.
Determination on the Coefficient of Thermal Expansion in High-Power InGaN-based Light-emitting Diodes by Optical Coherence Tomography
Authors: Lee Ya-Ju , Chou Chun-Yang , Huang Chun-Ying , Yao Yung-Chi , Haung Yi-Kai , Tsai Meng-Tsan 
Published: October 2017

AbstractThe coefficient of thermal expansion (CTE) is a physical quantity that indicates the thermal expansion value of a material upon heating. For advanced thermal management, the accurate and immediate determination of the CTE of packaging materials is gaining importance because the demand for high-power lighting-emitting diodes (LEDs) is currently increasing. In this study, we used optical coherence tomography (OCT) to measure the CTE of an InGaN-based (λ = 450 nm) high-power LED encapsulated in polystyrene resin. The distances between individual interfaces of the OCT images were observed and recorded to derive the instantaneous CTE of the packaged LED under different injected currents. The LED junction temperature at different injected currents was established with the forward voltage method. Accordingly, the measured instantaneous CTE of polystyrene resin varied from 5.86 × 10−5 °C−1 to 14.10 × 10−5 °C−1 in the junction temperature range 25–225 °C and exhibited a uniform distribution in an OCT scanning area of 200 × 200 μm. Most importantly, this work validates the hypothesis that OCT can provide an alternative way to directly and nondestructively determine the spatially resolved CTE of the packaged LED device, which offers significant advantages over traditional CTE measurement techniques.
Anti-obesity effect of a traditional Chinese dietary habit—blending lard with vegetable oil while cooking
Authors: Wang Ji , Yan Sisi , Xiao Haisi , Zhou Huijuan , Liu Shuiping , Zeng Yu , Liu Biying , Li Rongfang , Yuan Zhihang , Wu Jing , Yi Jine , Razack Yarou Bao Sero , Wen Lixin 
Published: October 2017

AbstractObesity, which is associated with dietary habits, has become a global social problem and causes many metabolic diseases. In China, both percentages of adult obesity and overweight are far lower compared to western countries. It was designed to increase the two levels of daily intake in human, namely 3.8% and 6.5%, which are recommendatory intake (25 g/d) and Chinese citizens’ practical intake (41.4 g/d), respectively. The mice were respectively fed with feeds added with soybean oil, lard or the oil blended by both for 12 weeks. In the mice fed with diet containing 3.8% of the three oils or 6.5% blended oil, their body weight, body fat rate, cross-sectional area of adipocytes, adipogenesis and lipogenesis in adipose were decreased, whereas hydrolysis of triglyserides in adipose was increased. This study demonstrated that the oil mixture containing lard and soybean oil had a remarkable anti-obesity effect. It suggests that the traditional Chinese dietary habits using oils blended with lard and soybean oil, might be one of the factors of lower percentages of overweight and obesity in China, and that the increasing of dietary oil intake and the changing of its component resulted in the increasing of obesity rate in China over the past decades.
Projective simulation with generalization
Authors: Melnikov Alexey A. , Makmal Adi , Dunjko Vedran , Briegel Hans J. 
Published: October 2017

AbstractThe ability to generalize is an important feature of any intelligent agent. Not only because it may allow the agent to cope with large amounts of data, but also because in some environments, an agent with no generalization capabilities cannot learn. In this work we outline several criteria for generalization, and present a dynamic and autonomous machinery that enables projective simulation agents to meaningfully generalize. Projective simulation, a novel, physical approach to artificial intelligence, was recently shown to perform well in standard reinforcement learning problems, with applications in advanced robotics as well as quantum experiments. Both the basic projective simulation model and the presented generalization machinery are based on very simple principles. This allows us to provide a full analytical analysis of the agent’s performance and to illustrate the benefit the agent gains by generalizing. Specifically, we show that already in basic (but extreme) environments, learning without generalization may be impossible, and demonstrate how the presented generalization machinery enables the projective simulation agent to learn.
Novel Benzylidene Thiazolidinedione Derivatives as Partial PPARγ Agonists and their Antidiabetic Effects on Type 2 Diabetes
Authors: Yasmin Sabina , Capone Fabio , Laghezza Antonio , Piaz Fabrizio Dal , Loiodice Fulvio , Vijayan Viswanathan , Devadasan Velmurugan , Mondal Susanta K. , Atlı Özlem , Baysal Merve , Pattnaik Ashok K. , Jayaprakash Venkatesan , Lavecchia Antonio 
Published: October 2017

AbstractPeroxisome proliferator-activated receptor γ (PPARγ) has received significant attention as a key regulator of glucose and lipid homeostasis. In this study, we synthesized and tested a library of novel 5-benzylidene-thiazolidin-2,4-dione (BTZD) derivatives bearing a substituent on nitrogen of TZD nucleus (compounds 1a-1k, 2i-10i, 3a, 6a, and 8a-10a). Three compounds (1a, 1i, and 3a) exhibited selectivity towards PPARγ and were found to be weak to moderate partial agonists. Surface Plasmon Resonance (SPR) results demonstrated binding affinity of 1a, 1i and 3a towards PPARγ. Furthermore, docking experiments revealed that BTZDs interact with PPARγ through a distinct binding mode, forming primarily hydrophobic contacts with the ligand-binding pocket (LBD) without direct H-bonding interactions to key residues in H12 that are characteristic of full agonists. In addition, 1a, 1i and 3a significantly improved hyperglycemia and hyperlipidaemia in streptozotocin-nicotinamide (STZ-NA)-induced diabetic rats at a dose of 36 mg/kg/day administered orally for 15 days. Histopathological investigations revealed that microscopic architecture of pancreatic and hepatic cells improved in BTZDs-treated diabetic rats. These findings suggested that 1a, 1i and 3a are very promising pharmacological agents by selectively targeting PPARγ for further development in the clinical treatment of type 2 diabetes mellitus.