bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunogenicity and functional characterization of Leishmania-derived hepatitis C virus envelope glycoprotein complex
Authors: Grzyb Katarzyna , Czarnota Anna , Brzozowska Agnieszka , Cieślik Anna , Rąbalski Łukasz , Tyborowska Jolanta , Bieńkowska-Szewczyk Krystyna 
Published: August 2016

AbstractHepatitis C virus (HCV) envelope glycoproteins E1 and E2 are the main inducers of a cross-neutralizing antibody response which plays an important role in the early phase of viral infection. Correctly folded and immunologically active E1E2 complex can be expressed in mammalian cells, though the production process might still prove restrictive, even if the immunological response of a vaccine candidate is positive. Here, we report a characterization and immunogenicity study of a full-length (fE1E2) and soluble version of the E1E2 complex (tE1E2) from genotype 1a, successfully expressed in the cells of Leishmania tarentolae. In a functional study, we confirmed the binding of both Leishmania-derived E1E2 complexes to the CD-81 receptor and the presence of the major epitopes participating in a neutralizing antibody response. Both complexes were proved to be highly immunogenic in mice and elicited neutralizing antibody response. Moreover, cross-reactivity of the mouse sera was detected for all tested HCV genotypes with the highest signal intensity observed for genotypes 1a, 1b, 5 and 6. Since the development of a prophylactic vaccine against HCV is still needed to control the global infection, our Leishmania-derived E1E2 glycoproteins could be considered a potential cost-effective vaccine candidate.
A likely inverse-Compton emission from the Type IIb SN 2013df
Authors: Li K. L. , Kong A. K. H. 
Published: August 2016

AbstractThe inverse-Compton X-ray emission model for supernovae has been well established to explain the X-ray properties of many supernovae for over 30 years. However, no observational case has yet been found to connect the X-rays with the optical lights as they should be. Here, we report the discovery of a hard X-ray source that is associated with a Type II-b supernova. Simultaneous emission enhancements have been found in both the X-ray and optical light curves twenty days after the supernova explosion. While the enhanced X-rays are likely dominated by inverse-Compton scatterings of the supernova’s lights from the Type II-b secondary peak, we propose a scenario of a high-speed supernova ejecta colliding with a low-density pre-supernova stellar wind that produces an optically thin and high-temperature electron gas for the Comptonization. The inferred stellar wind mass-loss rate is consistent with that of the supernova progenitor candidate as a yellow supergiant detected by the Hubble Space Telescope, providing an independent proof for the progenitor. This is also new evidence of the inverse-Compton emission during the early phase of a supernova.
Towards coherent combining of X-band high power microwaves: phase-locked long pulse radiations by a relativistic triaxial klystron amplifier
Authors: Ju Jinchuan , Zhang Jun , Qi Zumin , Yang Jianhua , Shu Ting , Zhang Jiande , Zhong Huihuang 
Published: August 2016

AbstractThe radio-frequency breakdown due to ultrahigh electric field strength essentially limits power handling capability of an individual high power microwave (HPM) generator and this issue becomes more challenging for high frequency bands. Coherent power combining therefore provides an alternative approach to achieve an equivalent peak power of the order of ∼100 GW, which consequently provides opportunities to explore microwave related physics at extremes. The triaxial klystron amplifier (TKA) is a promising candidate for coherent power combing in high frequency bands owing to its intrinsic merit of high power capacity, nevertheless phase-locked long pulse radiation from TKA has not yet been obtained experimentally as the coaxial structure of TKA can easily lead to self-excitation of parasitic modes. In this paper, we present investigations into an X-band TKA capable of producing 1.1 GW HPMs with pulse duration of about 103 ns at the frequency of 9.375 GHz in experiment. Furthermore, the shot-to-shot fluctuation standard deviation of the phase shifts between the input and output microwaves is demonstrated to be less than 10°. The reported achievements open up prospects for accomplishing coherent power combining of X-band HPMs in the near future and might also excite new development interests concerning high frequency TKAs.
Imatinib binding to human c-Src is coupled to inter-domain allostery and suggests a novel kinase inhibition strategy
Authors: Tsutsui Yuko , Deredge Daniel , Wintrode Patrick L. , Hays Franklin A. 
Published: August 2016

AbstractImatinib (Gleevec), a non-receptor tyrosine kinase inhibitor (nRTKI), is one of the most successful anti-neoplastic drugs in clinical use. However, imatinib-resistant mutations are increasingly prevalent in patient tissues and driving development of novel imatinib analogs. We present a detailed study of the conformational dynamics, in the presence and absence of bound imatinib, for full-length human c-Src using hydrogen-deuterium exchange and mass spectrometry. Our results demonstrate that imatinib binding to the kinase domain effects dynamics of proline-rich or phosphorylated peptide ligand binding sites in distal c-Src SH3 and SH2 domains. These dynamic changes in functional regulatory sites, distal to the imatinib binding pocket, show similarities to structural transitions involved in kinase activation. These data also identify imatinib-sensitive and imatinib-resistant, mutation sites. Thus, the current study identifies novel c-Src allosteric sites associated with imatinib binding and kinase activation and provide a framework for follow-on development of TKI binding modulators.
Small Molecular-Sized Artesunate Attenuates Ocular Neovascularization via VEGFR2, PKCα and PDGFR Targets
Authors: Zong Yao , Yuan Yongguang , Qian Xiaobing , Huang Zhen , Yang Wei , Lin Leilei , Zheng Qishan , Li Yujie , He Huining , Gao Qianying 
Published: August 2016

AbstractOcular neovascularization (NV) is the primary cause of blindness in many ocular diseases. Large molecular weight anti- vascular endothelial growth factor (VEGF) protein drugs, such as Avastin and Lucentis, have saved the vision of millions. However, approximately 20–30% of patients respond poorly to anti-VEGF treatment. We found that artesunate (ART), a small molecular derivative of artemisinin, had a significant inhibitory effect on ocular NV by downregulating the expression of VEGFR2, PKCα and PDGFR. ART significantly inhibited retinal NV in rabbits and macular edema in monkeys with greater anterior chamber penetrability and more durable efficacy than Avastin. Our pilot study showed that intravitreal injection of 80 μg ART significantly inhibited iris and corneal NV in a severe retinal detachment case. Our results suggest that ART might be a potential persistent small-molecule drug to manage ocular NV via multi-targets.
Prolactin Pro-Differentiation Pathway in Triple Negative Breast Cancer: Impact on Prognosis and Potential Therapy
Authors: López-Ozuna Vanessa M. , Hachim Ibrahim Y. , Hachim Mahmood Y. , Lebrun Jean-Jacques , Ali Suhad 
Published: August 2016

AbstractTriple negative breast cancer (TNBC) is a heterogeneous disease associated with poor clinical outcome and lack of targeted therapy. Here we show that prolactin (PRL) and its signaling pathway serve as a sub-classifier and predictor of pro-differentiation therapy in TNBC. Using immunohistochemistry and various gene expression in silica analyses we observed that prolactin receptor (PRLR) protein and mRNA levels are down regulated in TNBC cases. In addition, examining correlation of PRLR gene expression with metagenes of TNBC subtypes (580 cases), we found that PRLR gene expression sub-classifies TNBC patients into a new subgroup (TNBC-PRLR) characterized by epithelial-luminal differentiation. Importantly, gene expression of PRL signaling pathway components individually (PRL, PRLR, Jak2 and Stat5a), or as a gene signature is able to predict TNBC patients with significantly better survival outcomes. As PRL hormone is a druggable target we determined the biological role of PRL in TNBC biology. Significantly, restoration/activation of PRL pathway in TNBC cells representative of mesenchymal or TNBC-PRLR subgroups led to induction of epithelial phenotype and suppression of tumorigenesis. Altogether, these results offer potential new modalities for TNBC stratification and development of personalized therapy based on PRL pathway activation.
Metabolomics Profiling for Obstructive Sleep Apnea and Simple Snorers
Authors: Xu Huajun , Zheng Xiaojiao , Qian Yingjun , Guan Jian , Yi Hongliang , Zou Jianyin , Wang Yuyu , Meng Lili , Zhao Aihua , Yin Shankai , Jia Wei 
Published: August 2016

AbstractFew clinical studies have explored altered urinary metabolite levels in patients with obstructive sleep apnea (OSA). Thus, we applied a metabolomics approach to analyze urinary metabolites in three groups of participants: patients with polysomnography (PSG)-confirmed OSA, simple snorers (SS) and normal subjects. Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and gas chromatography coupled with time-of-flight mass spectrometry were used. A total of 21 and 31 metabolites were differentially expressed in the SS and OSA groups, respectively. Patients with OSA had 18 metabolites different from those with SS. Of the 56 metabolites detected among the 3 groups, 24 were consistently higher or lower. A receiver operator curve analysis revealed that the combination of 4-hydroxypentenoic acid, arabinose, glycochenodeoxycholate-3-sulfate, isoleucine, serine and xanthine produced a moderate diagnostic score with a sensitivity (specificity) of 75% (78%) for distinguishing OSA from those without OSA. The combination of 4-hydroxypentenoic acid, 5-dihydrotestosterone sulfate, serine, spermine and xanthine distinguished OSA from SS with a sensitivity of 85% and specificity of 80%. Multiple metabolites and metabolic pathways associated with SS and OSA were identified using the metabolomics approach and the altered metabolite signatures could potentially serve as an alternative diagnostic method to PSG.
Microbial metabolism mediates interactions between dissolved organic matter and clay minerals in streamwater
Authors: Hunter W. R. , Battin T. J. 
Published: August 2016

AbstractSorption of organic molecules to mineral surfaces is an important control upon the aquatic carbon (C) cycle. Organo-mineral interactions are known to regulate the transport and burial of C within inland waters, yet the mechanisms that underlie these processes are poorly constrained. Streamwater contains a complex and dynamic mix of dissolved organic compounds that coexists with a range of organic and inorganic particles and microorganisms. To test how microbial metabolism and organo-mineral complexation alter amino acid and organic carbon fluxes we experimented with 13C-labelled amino acids and two common clay minerals (kaolinite and montmorillonite). The addition of 13C-labelled amino acids stimulated increased microbial activity. Amino acids were preferentially mineralized by the microbial community, concomitant with the leaching of other (non-labelled) dissolved organic molecules that were removed from solution by clay-mediated processes. We propose that microbial processes mediate the formation of organo-mineral particles in streamwater, with potential implications for the biochemical composition of organic matter transported through and buried within fluvial environments.
Transcriptomic signatures of neuronal differentiation and their association with risk genes for autism spectrum and related neuropsychiatric disorders
Authors: Chiocchetti A G , Haslinger D , Stein J L , de la Torre-Ubieta L , Cocchi E , Rothämel T , Lindlar S , Waltes R , Fulda S , Geschwind D H , Freitag C M 
Published: August 2016

AbstractGenes for autism spectrum disorders (ASDs) are also implicated in fragile X syndrome (FXS), intellectual disabilities (ID) or schizophrenia (SCZ), and converge on neuronal function and differentiation. The SH-SY5Y neuroblastoma cell line, the most widely used system to study neurodevelopment, is currently discussed for its applicability to model cortical development. We implemented an optimal neuronal differentiation protocol of this system and evaluated neurodevelopment at the transcriptomic level using the CoNTeXT framework, a machine-learning algorithm based on human post-mortem brain data estimating developmental stage and regional identity of transcriptomic signatures. Our improved model in contrast to currently used SH-SY5Y models does capture early neurodevelopmental processes with high fidelity. We applied regression modelling, dynamic time warping analysis, parallel independent component analysis and weighted gene co-expression network analysis to identify activated gene sets and networks. Finally, we tested and compared these sets for enrichment of risk genes for neuropsychiatric disorders. We confirm a significant overlap of genes implicated in ASD with FXS, ID and SCZ. However, counterintuitive to this observation, we report that risk genes affect pathways specific for each disorder during early neurodevelopment. Genes implicated in ASD, ID, FXS and SCZ were enriched among the positive regulators, but only ID-implicated genes were also negative regulators of neuronal differentiation. ASD and ID genes were involved in dendritic branching modules, but only ASD risk genes were implicated in histone modification or axonal guidance. Only ID genes were over-represented among cell cycle modules. We conclude that the underlying signatures are disorder-specific and that the shared genetic architecture results in overlaps across disorders such as ID in ASD. Thus, adding developmental network context to genetic analyses will aid differentiating the pathophysiology of neuropsychiatric disorders.
An enzyme in the kynurenine pathway that governs vulnerability to suicidal behavior by regulating excitotoxicity and neuroinflammation
Authors: Brundin L , Sellgren C M , Lim C K , Grit J , Pålsson E , Landén M , Samuelsson M , Lundgren K , Brundin P , Fuchs D , Postolache T T , Traskman-Bendz L , Guillemin G J , Erhardt S 
Published: August 2016

AbstractEmerging evidence suggests that inflammation has a key role in depression and suicidal behavior. The kynurenine pathway is involved in neuroinflammation and regulates glutamate neurotransmission. In the cerebrospinal fluid (CSF) of suicidal patients, levels of inflammatory cytokines and the kynurenine metabolite quinolinic acid (QUIN), an N-methyl-d-aspartate receptor agonist, are increased. The enzyme amino-β-carboxymuconate-semialdehyde-decarboxylase (ACMSD) limits QUIN formation by competitive production of the neuroprotective metabolite picolinic acid (PIC). Therefore, decreased ACMSD activity can lead to excess QUIN. We tested the hypothesis that deficient ACMSD activity underlies suicidal behavior. We measured PIC and QUIN in CSF and plasma samples from 137 patients exhibiting suicidal behavior and 71 healthy controls. We used DSM-IV and the Montgomery-Åsberg Depression Rating Scale and Suicide Assessment Scale to assess behavioral changes. Finally, we genotyped ACMSD tag single-nucleotide polymorphisms (SNPs) in 77 of the patients and 150 population-based controls. Suicide attempters had reduced PIC and a decreased PIC/QUIN ratio in both CSF (P<0.001) and blood (P=0.001 and P<0.01, respectively). The reductions of PIC in CSF were sustained over 2 years after the suicide attempt based on repeated measures. The minor C allele of the ACMSD SNP rs2121337 was more prevalent in suicide attempters and associated with increased CSF QUIN. Taken together, our data suggest that increased QUIN levels may result from reduced activity of ACMSD in suicidal subjects. We conclude that measures of kynurenine metabolites can be explored as biomarkers of suicide risk, and that ACMSD is a potential therapeutic target in suicidal behavior.
N-linked glycosylation of N48 is required for equilibrative nucleoside transporter 1 (ENT1) function
Authors: Bicket Alex , Coe Imogen R. 
Published: August 2016

Human equilibrative nucleoside transporter 1 (hENT1) transports nucleosides and nucleoside analogue drugs across cellular membranes and is necessary for the uptake of many anti-cancer, anti-parasitic and anti-viral drugs. Previous work, and in silico prediction, suggest that hENT1 is glycosylated at Asn48 in the first extracellular loop of the protein and that glycosylation plays a role in correct localization and function of hENT1. Site-directed mutagenesis of wild-type (wt) hENT1 removed potential glycosylation sites. Constructs (wt 3xFLAG-hENT1, N48Q-3xFLAG-hENT1 or N288Q-3xFLAG-hENT2) were transiently transfected into HEK293 cells and cell lysates were treated with or without peptide–N-glycosidase F (PNGase-F), followed by immunoblotting analysis. Substitution of N48 prevents hENT1 glycosylation, confirming a single N-linked glycosylation site. N48Q-hENT1 protein is found at the plasma membrane in HEK293 cells but at lower levels compared with wt hENT1 based on S-(4-nitrobenzyl)-6-thioinosine (NBTI) binding analysis (wt 3xFLAG-ENT1 Bmax, 41.5±2.9 pmol/mg protein; N48Q-3xFLAG-ENT1 Bmax, 13.5±0.45 pmol/mg protein) and immunofluorescence microscopy. Although present at the membrane, chloroadenosine transport assays suggest that N48Q-hENT1 is non-functional (wt 3xFLAG-ENT1, 170.80±44.01 pmol/mg protein; N48Q-3xFLAG-ENT1, 57.91±17.06 pmol/mg protein; mock-transfected 74.31±19.65 pmol/mg protein). Co-immunoprecipitation analyses suggest that N48Q ENT1 is unable to interact with self or with wt hENT1. Based on these data we propose that glycosylation at N48 is critical for the localization, function and oligomerization of hENT1.
Independence of events, and errors in understanding it
Authors: Roney Chris 
Published: August 2016

AbstractThis article outlines errors that may occur when people predict event outcomes. The focus is on how our tendency to perceive independent events as connected, consistent with tenets of Gestalt Psychology, biases our expectations. Two well-documented phenomena that occur when people make predictions after a run of a particular outcome—the “gambler’s fallacy” and the “hot hand”—are used to illustrate the issue, and research is presented that highlights the importance of misperceptions of independence. Novel implications and hypotheses are presented that are generated from use of this gestalt approach.
Trading experience modulates anterior insula to reduce the endowment effect
Authors: Tong Lester C. P. , Ye Karen J. , Asai Kentaro , Ertac Seda , List John A. , Nusbaum Howard C. , Hortaçsu Ali 
Published: August 2016

SignificanceTrading experience has been shown to reduce the endowment effect, a decision-making bias that distorts market prices and reduces trade. Understanding the mechanisms underlying how experience changes this bias will provide important insights for developing interventions to improve market efficiency. Using functional magnetic resonance imaging, we show that market experience causes a reduction in right anterior insula activation during selling, which mediates a decrease in the endowment effect. These findings suggest that trading mitigates negative affective responses in the context of selling.
Water-soluble cavitands promote hydrolyses of long-chain diesters
Authors: Shi Qixun , Mower Matthew P. , Blackmond Donna G. , Rebek Julius 
Published: August 2016

Significance
Molecules in confined spaces behave differently from those in bulk solution and a number of container (host) compounds have been developed to exploit the differences. In aqueous media, hydrophobic forces can drive binding of guests into the limited space of container hosts, and flexible guests assume shapes congruent with the container’s space. Long-chain hydrocarbons take on folded conformations, which bring the guest’s ends closer together. Sites that are remote in bulk solution are no longer so in the complex; the sites become “entangled” and affect each other’s reactivity. Product distributions that are statistically determined in solution are significantly altered in cavitands and lead to enhanced yields of desired reaction products.
Increased incidence of infective endocarditis after the 2009 European Society of Cardiology guideline update: a nationwide study in the Netherlands
Authors: van den Brink Floris S. , Swaans Martin J. , Hoogendijk Mark G. , Alipour Arash , Kelder Johannes C. , Jaarsma Wybren , Eefting Frank D. , Groenmeijer Bjorn , Kupper A. Jon Funke , ten Berg Jurrien M. 
Published: August 2016

Aims
After the introduction of the European Society of Cardiology (ESC) guidelines on prevention, diagnosis, and treatment of infective endocarditis (IE) in 2009, prophylaxis for patients at risk became less strict. We hypothesize that there will be a rise in IE after the introduction of the guideline update.

Methods and Results
We performed a nationwide retrospective trend study using segmented regression analysis of the interrupted time series. The patient data were obtained via the national healthcare insurance database, which collects all the diagnoses nationwide. We compared the data before and after the introduction of the 2009 ESC guideline. Between 2005 and 2011, a total of 5213 patients were hospitalized with IE in the Netherlands. During this period, there was a significant increase in IE from 30.2 new cases per 1 000 000 in 2005 to 62.9 cases per 1 000 000 in 2011 (P &lt; 0.001). In 2009, the incidence of IE increased significantly above the projected historical trend (rate ratio: 1.327, 95% CI: 1.205–1.462; P &lt; 0.001). This coincides with the introduction of the 2009 ESC guideline. After the introduction of the ESC guideline, the streptococci-positive cultures increased significantly in the following years 2010–11 from 31.1 to 53.2% (P = 0.0031).

Conclusion
This observational study shows that there has been a steady increase in the IE incidence between 2005 and 2011. After the introduction of the 2009 ESC guidelines, the incidence increased more than expected from previous historical trends. Furthermore, there was a significant increase in streptococci-related IE cases.