bluuebunny/crossref_metadata_2025_split huggingface dataset:
First objective evaluation of taste sensitivity to 6-n-propylthiouracil (PROP), a paradigm gustatory stimulus in humans
Authors: Sollai Giorgia , Melis Melania , Pani Danilo , Cosseddu Piero , Usai Ilenia , Crnjar Roberto , Bonfiglio Annalisa , Tomassini Barbarossa Iole 
Published: January 2017

AbstractPractical and reliable methods for the objective measure of taste function are critically important for studying eating behavior and taste function impairment. Here, we present direct measures of human gustatory response to a prototypical bitter compound, 6-n-propyltiouracil (PROP), obtained by electrophysiological recordings from the tongue of subjects who were classified for taster status and genotyped for the specific receptor gene (TAS2R38), and in which taste papilla density was determined. PROP stimulation evoked negative slow potentials that represent the summated depolarization of taste cells. Depolarization amplitude and rate were correlated with papilla density and perceived bitterness, and associated with taster status and TAS2R38. Our study provides a robust and generalizable research tool for the quantitative measure of peripheral taste function, which can greatly help to resolve controversial outcomes on the PROP phenotype role in taste perception and food preferences, and be potentially useful for evaluating nutritional status and health.
Insights into an evolutionary strategy leading to antibiotic resistance
Authors: Hou Chun-Feng D. , Liu Jian-wei , Collyer Charles , Mitić Nataša , Pedroso Marcelo Monteiro , Schenk Gerhard , Ollis David L. 
Published: January 2017

AbstractMetallo-β-lactamases (MBLs) with activity towards a broad-spectrum of β-lactam antibiotics have become a major threat to public health, not least due to their ability to rapidly adapt their substrate preference. In this study, the capability of the MBL AIM-1 to evade antibiotic pressure by introducing specific mutations was probed by two alternative methods, i.e. site-saturation mutagenesis (SSM) of active site residues and in vitro evolution. Both approaches demonstrated that a single mutation in AIM-1 can greatly enhance a pathogen’s resistance towards broad spectrum antibiotics without significantly compromising the catalytic efficiency of the enzyme. Importantly, the evolution experiments demonstrated that relevant amino acids are not necessarily in close proximity to the catalytic centre of the enzyme. This observation is a powerful demonstration that MBLs have a diverse array of possibilities to adapt to new selection pressures, avenues that cannot easily be predicted from a crystal structure alone.
Extreme weather caused by concurrent cyclone, front and thunderstorm occurrences
Authors: Dowdy Andrew J. , Catto Jennifer L. 
Published: January 2017

AbstractPhenomena such as cyclones, fronts and thunderstorms can cause extreme weather in various regions throughout the world. Although these phenomena have been examined in numerous studies, they have not all been systematically examined in combination with each other, including in relation to extreme precipitation and extreme winds throughout the world. Consequently, the combined influence of these phenomena represents a substantial gap in the current understanding of the causes of extreme weather events. Here we present a systematic analysis of cyclones, fronts and thunderstorms in combination with each other, as represented by seven different types of storm combinations. Our results highlight the storm combinations that most frequently cause extreme weather in various regions of the world. The highest risk of extreme precipitation and extreme wind speeds is found to be associated with a triple storm type characterized by concurrent cyclone, front and thunderstorm occurrences. Our findings reveal new insight on the relationships between cyclones, fronts and thunderstorms and clearly demonstrate the importance of concurrent phenomena in causing extreme weather.
MiR-488 inhibits proliferation and cisplatin sensibility in non-small-cell lung cancer (NSCLC) cells by activating the eIF3a-mediated NER signaling pathway
Authors: Fang Chao , Chen Yi-Xin , Wu Na-Yiyuan , Yin Ji-Ye , Li Xiang-Ping , Huang Hsuan-Shun , Zhang Wei , Zhou Hong-Hao , Liu Zhao-Qian 
Published: January 2017

AbstractOur previous studied indicated that eukaryotic translation initiation factor 3a (eIF3a) increases the sensitive of platinum-based chemotherapy in lung cancer. MiRNAs play an important role in lung carcinogenesis and drug response. In this study, we aimed to identify potential endogenous miRNAs that inhibit eIF3a expression and determine their influence of this inhibition on cisplatin resistance. Using bioinformatics analysis prediction and confirmation with dual-luciferase reporter assays, we found that miRNA-488 inhibited eIF3a expression by directly binding to the 3’UTR of eIF3a. In addition, the overexpression of miRNA-488 inhibited cell migration and invasion in A549 cells, and also inhibited cell proliferation, cell cycle progression by elevated P27 expression. Compared to the parental cell line, A549/cisplatin (DDP) resistant cells exhibited a higher level of miRNA-488. Moreover, we found that miRNA-488 was associated with cisplatin resistance in three NSCLC cells (A549, H1299 and SK-MES-1). The mechanism of miRNA-488 induced cisplatin resistance was that miRNA-488 activated nucleotide excision repair (NER) by increasing the expression of Replication Protein A (RPA) 14 and Xeroderma pigmentosum group C (XPC). In conclusion, our results demonstrated that miRNA-488 is a tumor suppressor miRNA that acts by targeting eIF3a. Moreover, miRNA-488 also participates in eIF3a mediated cisplatin resistance in NSCLC cells.
Modeling confirmation bias and polarization
Authors: Del Vicario Michela , Scala Antonio , Caldarelli Guido , Stanley H. Eugene , Quattrociocchi Walter 
Published: January 2017

AbstractOnline users tend to select claims that adhere to their system of beliefs and to ignore dissenting information. Confirmation bias, indeed, plays a pivotal role in viral phenomena. Furthermore, the wide availability of content on the web fosters the aggregation of likeminded people where debates tend to enforce group polarization. Such a configuration might alter the public debate and thus the formation of the public opinion. In this paper we provide a mathematical model to study online social debates and the related polarization dynamics. We assume the basic updating rule of the Bounded Confidence Model (BCM) and we develop two variations a) the Rewire with Bounded Confidence Model (RBCM), in which discordant links are broken until convergence is reached; and b) the Unbounded Confidence Model, under which the interaction among discordant pairs of users is allowed even with a negative feedback, either with the rewiring step (RUCM) or without it (UCM). From numerical simulations we find that the new models (UCM and RUCM), unlike the BCM, are able to explain the coexistence of two stable final opinions, often observed in reality. Lastly, we present a mean field approximation of the newly introduced models.
EID3 directly associates with DNMT3A during transdifferentiation of human umbilical cord mesenchymal stem cells to NPC-like cells
Authors: Luo Liang , Chen Wen-Jin , Yin James Q. , Xu Ru-Xiang 
Published: January 2017

AbstractThere has been recently been increased interest in the plasticity of human umbilical cord mesenchymal stem cells (UMSCs) and their potential in the treatment of neurological disorders. In this study, UMSCs were transdifferentiated into neural stem-like cells (uNSCL), these cells grow in neurosphere-like structures and express high levels of NSCs markers. Epigenetics-related gene screening was here used to assess the relationship between E1A-like inhibitor of differentiation 3 (EID3), a p300 inhibitor, and DNA methyltransferase 3 A (DNMT3A) during the transdifferentiation of UMSCs into uNSCL in vitro. Before transdifferentiation of UMSCs into uNSCLs, high levels of EID3 and low levels of DNMT3A were detected; after transdifferentiation, low levels of EID3 and high levels of DNMT3A were detected. The current work showed that EID3 and DNMT3A co-localized in cell nuclei and EID3 interacted directly with DNMT3A in uNSCL. In summary, these results suggest that DNMT3A is probably directly regulated by EID3 during UMSC transdifferentiation into uNSCLs. These findings indicated a novel mechanism by which EID3, a p300 acetyltransferase inhibitor, could directly affect DNMT3A, this enzyme possesses dual methylation and demethylation abilities. These studies may be helpful for understanding a complex regulation mode of DNMT3A, which is a unique member of the methyltransferase family.
Circulating T lymphocyte subsets, cytokines, and immune checkpoint inhibitors in patients with bipolar II or major depression: a preliminary study
Authors: Wu Wei , Zheng Ya-li , Tian Li-ping , Lai Jian-bo , Hu Chan-chan , Zhang Peng , Chen Jing-kai , Hu Jian-bo , Huang Man-li , Wei Ning , Xu Wei-juan , Zhou Wei-hua , Lu Shao-jia , Lu Jing , Qi Hong-li , Wang Dan-dan , Zhou Xiao-yi , Duan Jin-feng , Xu Yi , Hu Shao-hua 
Published: January 2017

AbstractThis study aimed to investigate the less known activation pattern of T lymphocyte populations and immune checkpoint inhibitors on immunocytes in patients with bipolar II disorder depression (BD) or major depression (MD). A total of 23 patients with BD, 22 patients with MD, and 20 healthy controls (HCs) were recruited. The blood cell count of T lymphocyte subsets and the plasma level of cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) were selectively investigated. The expression of T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), programmed cell death protein 1 (PD-1) and its ligands, PD-L1 and PD-L2, on T lymphocytes and monocytes, was detected. In results, blood proportion of cytotoxic T cells significantly decreased in BD patients than in either MD patients or HCs. The plasma level of IL-6 increased in patients with BD and MD. The expression of TIM-3 on cytotoxic T cells significantly increased, whereas the expression of PD-L2 on monocytes significantly decreased in patients with BD than in HCs. These findings extended our knowledge of the immune dysfunction in patients with affective disorders.
Auditory Localisation Biases Increase with Sensory Uncertainty
Authors: Garcia Sara E. , Jones Pete R. , Rubin Gary S. , Nardini Marko 
Published: January 2017

AbstractPsychophysical studies have frequently found that adults with normal hearing exhibit systematic errors (biases) in their auditory localisation judgments. Here we tested (i) whether systematic localisation errors could reflect reliance on prior knowledge, as has been proposed for other systematic perceptual biases, and (ii) whether auditory localisation biases can be reduced following training with accurate visual feedback. Twenty-four normal hearing participants were asked to localise the position of a noise burst along the azimuth before, during, and after training with visual feedback. Consistent with reliance on prior knowledge to reduce sensory uncertainty, we found that auditory localisation biases increased when auditory localisation uncertainty increased. Specifically, participants mis-localised auditory stimuli as being more eccentric than they were, and did so more when auditory uncertainty was greater. However, biases also increased with eccentricity, despite no corresponding increase in uncertainty, which is not readily explained by use of a simple prior favouring peripheral locations. Localisation biases decreased (improved) following training with visual feedback, but the reliability of the visual feedback stimulus did not change the effects of training. We suggest that further research is needed to identify alternative mechanisms, besides use of prior knowledge, that could account for increased perceptual biases under sensory uncertainty.
Hydroxysafflor yellow A attenuates the expression of inflammatory cytokines in acute soft tissue injury
Authors: Dong Fang , Xue Changjiang , Wang Yu , Peng Yuanyuan , Zhang Yadan , Jin Ming , Zang Baoxia 
Published: January 2017

AbstractWe examined the effect of hydroxysafflor yellow A (HSYA) on the inflammatory response to strike-induced acute soft tissue injury in rats. Soft tissue injury was induced in rat leg muscles using a strike hammer, followed by intraperitoneal administration of HSYA at 16, 32, or 64 mg/kg. After 24 h, the rats were anaesthetized, blood and muscle samples were taken. Plasma levels of interleukin (IL)-6, IL-1β, and tumour necrosis factor (TNF)-αwere measured by enzyme-linked immunosorbent assay. Total RNA and protein were isolated from muscle tissue to determine the mRNA levels of IL-6, IL-1β, TNF-α, vascular cell adhesion molecule (VCAM)-1, and intercellular adhesion molecule (ICAM)-1, and the protein level of phosphorylated p38 mitogen-activated protein kinase (MAPK). Nuclear factor (NF)-κB expression was determined by muscle histopathology and immunohistochemistry. HSYA attenuated pathologic changes instrike-induced soft tissue inflammation. Treatment with HSYA also alleviated strike-induced increases in TNF-α, IL-1β, IL-6, VCAM-1, and ICAM-1mRNA levels and inhibited the increased activation of NF-κB and phosphorylation of p38 MAPK in muscle tissue. These findings suggest that HSYA effectively inhibits strike-induced inflammatory signal transduction in rats.
Myosin phosphatase and RhoA-activated kinase modulate arginine methylation by the regulation of protein arginine methyltransferase 5 in hepatocellular carcinoma cells
Authors: Sipos Adrienn , Iván Judit , Bécsi Bálint , Darula Zsuzsanna , Tamás István , Horváth Dániel , Medzihradszky Katalin F. , Erdődi Ferenc , Lontay Beáta 
Published: January 2017

AbstractMyosin phosphatase (MP) holoenzyme is a protein phosphatase-1 (PP1) type Ser/Thr specific enzyme that consists of a PP1 catalytic (PP1c) and a myosin phosphatase target subunit-1 (MYPT1). MYPT1 is an ubiquitously expressed isoform and it targets PP1c to its substrates. We identified the protein arginine methyltransferase 5 (PRMT5) enzyme of the methylosome complex as a MYPT1-binding protein uncovering the nuclear MYPT1-interactome of hepatocellular carcinoma cells. It is shown that PRMT5 is regulated by phosphorylation at Thr80 by RhoA-associated protein kinase and MP. Silencing of MYPT1 increased the level of the PRMT5-specific symmetric dimethylation on arginine residues of histone 2 A/4, a repressing gene expression mark, and it resulted in a global change in the expression of genes affecting cellular processes like growth, proliferation and cell death, also affecting the expression of the retinoblastoma protein and c-Myc. The phosphorylation of the MP inhibitory MYPT1T850 and the regulatory PRMT5T80 residues as well as the symmetric dimethylation of H2A/4 were elevated in human hepatocellular carcinoma and in other types of cancers. These changes correlated positively with the grade and state of the tumors. Our results suggest the tumor suppressor role of MP via inhibition of PRMT5 thereby regulating gene expression through histone arginine dimethylation.
Transcription factor Xpp1 is a switch between primary and secondary fungal metabolism
Authors: Derntl Christian , Kluger Bernhard , Bueschl Christoph , Schuhmacher Rainer , Mach Robert L. , Mach-Aigner Astrid R. 
Published: January 2017

Significance
Fungi produce a vast number of different chemical compounds via secondary metabolism. These compounds are of great interest because of their potential applicability in medicine, pharmacy, and biotechnology. In addition, a number of such compounds are toxins that potentially represent severe threats to human and animal health. However, under standard cultivation conditions, fungal secondary metabolism remains largely inactive. Here, we show that the deletion of the regulator Xylanase promoter binding protein 1 (Xpp1) results in the production of significantly more secondary metabolites in terms of both number and concentration. Because homologs of Xpp1 exist in fungi with numerous bioactive secondary metabolites, our results can lead to the discovery of secondary metabolites.
Different clades and traits yield similar grassland functional responses
Authors: Forrestel Elisabeth J. , Donoghue Michael J. , Edwards Erika J. , Jetz Walter , du Toit Justin C. O. , Smith Melinda D. 
Published: January 2017

SignificancePlant functional traits—characteristics that influence performance or fitness—are increasingly being used to model important ecosystem properties such as primary production. These approaches assume that traits confer specific functions or responses under given environmental conditions, and that these trait–environment and trait–function relationships can be generalized globally irrespective of a region's history or differences in species assemblages. Here, we test this assumption in grasslands with distinct histories and find that different combinations of trait values can yield similar productivity–precipitation relationships. Our study highlights a missing link in the development of trait-based approaches to modeling ecosystem function, namely that there is not necessarily a single solution or set of traits that yields higher function in a given environment.
Redox crisis underlies conditional light–dark lethality in cyanobacterial mutants that lack the circadian regulator, RpaA
Authors: Diamond Spencer , Rubin Benjamin E. , Shultzaberger Ryan K. , Chen You , Barber Chase D. , Golden Susan S. 
Published: January 2017

SignificanceThe evolution of photosynthetic cyanobacteria under 24-h cycles of light and darkness selected for a robust circadian clock. Understanding how cyanobacteria integrate circadian clock signals with natural light–dark cycles to control metabolism is critical, because these organisms are central to global carbon cycling and hold promise for development of renewable energy. Here we assess how the circadian transcription factor regulator of phycobilisome association A (RpaA) influences metabolism as a cyanobacterium goes through a light-to-dark transition. The data show that RpaA plays a key role in maintaining metabolic stability during the night period. Additionally, RpaA is important in controlling redox balance, which in turn is very important for regulating metabolism at night.
Iconic photographs and the ebb and flow of empathic response to humanitarian disasters
Authors: Slovic Paul , Västfjäll Daniel , Erlandsson Arvid , Gregory Robin 
Published: January 2017

SignificanceWe cannot assume that the statistics of mass human crises will capture our attention or move us to take action, no matter how large the numbers. The data that we present show that the world was basically asleep as the body count in the Syrian war rose steadily into the hundreds of thousands. The iconic image of a young Syrian child, lying face-down on a beach, woke the world for a brief time, bringing much-needed attention to the war and the plight of its many victims. But this empathic response was short-lived. We outline the need for better laws, institutions, and decision-making procedures to channel empathy into appropriate and effective humanitarian actions by individuals and their governments.
A second decoupling between merging binary black holes and the inner disc – impact on the electromagnetic counterpart
Authors: Fontecilla Camilo , Chen Xian , Cuadra Jorge 
Published: January 2017

Abstract
The coalescence of two supermassive black holes (SMBHs) produces powerful gravitational wave radiation and, if gas is present in the vicinity, also an electromagnetic (EM) counterpart. In the standard picture, an EM outburst will be produced when the binary ‘decouples’ from the circum-binary disc and starts ‘squeezing’ the disc inside the secondary orbit, resulting in its quick accretion on to the primary black hole. Here, we use analytical arguments and numerical simulations to show that the disc within about 20 RS of an SMBH survives the merger without being depleted. The reason is a ‘second decoupling’: the inner disc thickens due to tidal heating and inefficient cooling, effectively decoupling from the interaction of the binary. We show that this second decoupling quenches the heating sources in the disc ${\cal O}(10^2)$ d before coalescence. This will render the peak UV/X-ray luminosity significantly weaker than previously thought. After the merger, the residual disc cools down and expands, merging with the outer disc rather than being completely accreted. This results in continuous EM emission, hindering the detection of the cut-off and re-brightening proposed in earlier studies.
Development and Underdevelopment in the Middle East and North Africa
Authors: Cammett Melani 
Published: January 2017

AbstractThis article examines the trajectories of economic development and underdevelopment in the Middle East and North Africa (MENA). It first considers the empirical record of development in the region, paying particular attention to standard measures of GDP, industrialization, and social development. The article contextualizes the region’s development trajectory in a larger set of cross-regional comparisons and looks at the region’s record of economic growth and development in different periods after World War II. It also evaluates a number of factors that account for economic performance in the region—such as colonialism, Islam, social relations, corruption and crony capitalism, authoritarianism, and populism—before offering an alternative account. It argues that the MENA’s suboptimal economic performance is associated with the particular manifestation of business–government relations in the region.
Ballet Bawdies and Dancing Ducks
Authors: Schwadron Hannah 
Published: January 2017

Abstract
This article examines the dancing joke-work of Jewish film stars as ballet swans in Be Yourself and Funny Girl. It shows how the joke of the Jewish swan queers white heterosexual femininity while revealing the sustained power of its classical Western-centric swan tropes. In situating Jewish swan humor within theories of parody, queer discourse, and gendered joke-work, the article highlights the pleasurable embodiment of enduring Jewish female stereotypes and reveals a comic dance legacy of the funny girl body unfit for love. It also explains how the humor of ballet parody and the swan constructs the Jewish funny girl body; how Be Yourself and Funny Girl stake a claim in ethnic and sexual otherness as sites of comic expression and critical difference; and how each film embodies critiques of classical ballet and its idealist proscriptions for white women even as both sustain romantic fantasies of female leads.