bluuebunny/crossref_metadata_2025_split huggingface dataset:
MIF gene rs755622 polymorphism positively associated with acute coronary syndrome in Chinese Han population: case–control study
Authors: Du Guo-Li , Luo Jun-Yi , Wang Duolao , Li Yan-Hong , Fang Bin-Bin , Li Xiao-Mei , Gao Xiao-Ming , Yang Yi-Ning 
Published: January 2020

AbstractMacrophage migration inhibitory factor (MIF) has been recognized as a major player in the pathogenesis of atherosclerosis. This study determined the association between polymorphisms of MIF gene and acute coronary syndrome (ACS). The polymorphism of MIF gene (rs755622, rs1007888 and rs2096525) was analyzed in 1153 healthy controls and 699 ACS cases in Chinese Han population. Plasma MIF level was also measured in part of ACS patients (139/19.9%) and healthy controls (129/11.2%) randomly. Most participants including healthy controls and ACS patients carried rs755622 GG (63.1% vs. 56.7%) and CG genotypes (33.1% vs. 38.9%) and G allele of rs755622 (79.6% vs. 76.1%, respectively), while CC genotype (3.8% vs. 4.4%) and C allele (20.4% vs. 23.9%) carriers were the lowest. Multivariate logistic regression analysis showed that carriers with rs755622 C allele had a higher risk of ACS compared to other genotypes (AOR = 1.278, 95% CI: 1.042–1.567). In addition, CC genotype carriers had the highest plasma levels of MIF than other genotype carriers. The MIF level in ACS patients with CC genotype was significantly higher than ACS patients carrying GG genotype and healthy controls carrying 3 different genotypes of MIF gene rs755622. Our findings indicate that MIF gene rs755622 variant C allele is associated with increased risk of ACS. Identification of this MIF gene polymorphism may help for predicting the risk of ACS.
Experimental glaucoma model with controllable intraocular pressure history
Authors: Ficarrotta Kayla R. , Mohamed Youssef H. , Passaglia Christopher L. 
Published: January 2020

AbstractGlaucoma-like neuropathies can be experimentally induced by disturbing aqueous outflow from the eye, resulting in intraocular pressure (IOP) changes that are variable in magnitude and time course and permanent in duration. This study introduces a novel method of glaucoma induction that offers researchers round-the-clock measurement and reversible control of IOP for the first time. One eye of Brown-Norway rats was implanted with a cannula tethered to a pressure sensor and aqueous reservoir. IOP was raised 10 mmHg for weeks-to-months in treated animals and unaltered in control animals. Counts of Brn3a-expressing retinal ganglion cells (RGCs) in implanted eyes were indistinguishable from non-implanted eyes in control animals and 15 ± 2%, 23 ± 4%, and 38 ± 4% lower in animals exposed to 2, 4, and 9 weeks of IOP elevation. RGC loss was greater in peripheral retina at 2 weeks and widespread at longer durations. Optic nerves also showed progressive degeneration with exposure duration, yet conventional outflow facility of implanted eyes was normal (24.1 ± 2.9 nl/min/mmHg) even after 9-weeks elevation. Hence, this infusion-based glaucoma model exhibits graded neural damage with unimpaired outflow pathways. The model further revealed a potentially-significant finding that outflow properties of rat eyes do not remodel in response to chronic ocular hypertension.
Structures of β-glycosidase LXYL-P1-2 reveals the product binding state of GH3 family and a specific pocket for Taxol recognition
Authors: Yang Lin , Chen Tian-Jiao , Wang Fen , Li Li , Yu Wen-Bo , Si Yi-Kang , Chen Jing-Jing , Liu Wan-Cang , Zhu Ping , Gong Weimin 
Published: January 2020

AbstractLXYL-P1-2 is one of the few xylosidases that efficiently catalyze the reaction from 7-β-xylosyl-10-deacetyltaxol (XDT) to 10-deacetyltaxol (DT), and is a potential enzyme used in Taxol industrial production. Here we report the crystal structure of LXYL-P1-2 and its XDT binding complex. These structures reveal an enzyme/product complex with the sugar conformation different from the enzyme/substrate complex reported previously in GH3 enzymes, even in the whole glycohydrolases family. In addition, the DT binding pocket is identified as the structural basis for the substrate specificity. Further structure analysis reveals common features in LXYL-P1-2 and Taxol binding protein tubulin, which might provide useful information for designing new Taxol carrier proteins for drug delivery.
The PHD finger of Arabidopsis SIZ1 recognizes trimethylated histone H3K4 mediating SIZ1 function and abiotic stress response
Authors: Miura Kenji , Renhu Na , Suzaki Takuya 
Published: January 2020

AbstractArabidopsis SIZ1 encodes a SUMO E3 ligase to regulate abiotic and biotic stress responses. Among SIZ1 or mammalian PIAS orthologs, plant SIZ1 proteins contain the plant homeodomain (PHD) finger, a C4HC3 zinc finger. Here, we investigated the importance of PHD of Arabidopsis SIZ1. The ProSIZ1::SIZ1(ΔPHD):GFP was unable to complement growth retardation, ABA hypersensitivity, and the cold-sensitive phenotype of the siz1 mutant, but ProSIZ1::SIZ1:GFP could. Substitution of C162S in the PHD finger was unable to complement the siz1 mutation. Tri-methylated histone H3K4 (H3K4me3) was recognized by PHD, not by PHD(C162S). WRKY70 was up-regulated in the siz1-2 mutant and H3K4me3 accumulated at high levels in the WRKY70 promoter. PHD interacts with ATX, which mediates methylation of histone, probably leading to suppression of ATX’s function. These results suggest that the PHD finger of SIZ1 is important for recognition of the histone code and is required for SIZ1 function and transcriptional suppression.
Up-regulation of P21-activated kinase 1 in osteoarthritis chondrocytes is responsible for osteoarthritic cartilage destruction
Authors: Ma Wanli , Wang Xiaohe , Wang Chunhui , Gong Mingzhi , Ren Peng 
Published: January 2020

Abstract
Osteoarthritis is mainly caused by a degenerative joint disorder, which is characterized by the gradual degradation of articular cartilage and synovial inflammation. The chondrocyte, the unique resident cell type of articular cartilage, is crucial for the development of osteoarthritis. Previous studies revealed that P21-activated kinase-1 (PAK1) was responsible for the initiation of inflammation. The purpose of the present study was to determine the potential role of PAK1 in osteoarthritis. The level of PAK1 expression was measured by Western blot and quantitative real-time PCR in articular cartilage from osteoarthritis model rats and patients with osteoarthritis. In addition, the functional role of aberrant PAK1 expression was detected in the chondrocytes. We found that the expression of PAK1 was significantly increased in chondrocytes treated with osteoarthritis-related factors. Increased expression of PAK1 was also observed in knee articular cartilage samples from patients with osteoarthritis and osteoarthritis model rats. PAK1 was found to inhibit chondrocytes proliferation and to promote the production of inflammatory cytokines in cartilages chondrocytes. Furthermore, we found that PAK1 modulated the production of extracellular matrix and cartilage degrading enzymes in chondrocytes. Results of the present studies demonstrated that PAK1 might play an important role in the pathogenesis of osteoarthritis.
Long non-coding RNA FGD5-AS1 promotes non-small cell lung cancer cell proliferation through sponging hsa-miR-107 to up-regulate FGFRL1
Authors: Fan Yafeng , Li Hongxia , Yu Zhongping , Dong Wen , Cui Xiaoyan , Ma Jinlian , Li Shengwen 
Published: January 2020

Abstract
Long non-coding RNA (lncRNA) FYVE, RhoGEF and PH domain containing 5 antisense RNA 1 (FGD5-AS1) has been reported as an oncogene in colorectal cancer, promoting its tumorgenesis. The present paper focused on searching the potential function of FGD5-AS1 in non-small cell lung carcinoma (NSCLC). There are connections between the expression of lncRNA FGD5-AS1 and human NSCLC tumor growth and progression. Also, the relationships between FGD5-AS1, hsa-miR-107 and mRNA fibroblast growth factor receptor like 1 (FGFRL1) are going to test their interaction in NSCLC cell lines, which may cause a series of biological behaviors of NSCLC cells. qRT-PCR analysis was conducted to test the expression of RNAs in different situation. CCK-8 experiment and clone formation assay were performed to assess proliferation of NSCLC cells. Also, connection between FGD5-AS1 and hsa-miR-107 were investigated by luciferase reporter assay and RNA pull-down assay. Rescue experiments were performed to verify the modulating relationship between FGD5-AS1, hsa-miR-107 and FGFRL1. High-level expression of FGD5-AS1 was found in NSCLC. FGD5-AS1 may promote the proliferation of NSCLC cells. Also, the combination between hsa-miR-107, FGD5-AS1 and NSCLC have been proved, which means they can play an interaction function in NSCLC cells. Thence, we concluded that lncRNA FGD5-AS1 promotes non-small cell lung cancer cell proliferation through sponging hsa-miR-107 to up-regulate FGFRL1.
Type 2 inflammation suppression by T-regulatory cells attenuates the eosinophil recruitment in mucosa of chronic sinusitis
Authors: Chang Lihong , Wang Zhiyuan , Li Shuaixiang , Chen Xiaohong , Li Xia , Zhao Jun , Lai Xiaoping , Huang Jiancong , Wu Xifu , Huang Zizhen , Bellanti Joseph A. , Zheng Song Guo , Zhang Gehua 
Published: January 2020

Abstract
Type 2 inflammation and eosinophilic infiltration are prominent pathologic features of chronic rhinosinusitis with nasal polyps (CRSwNP). The purpose of the present study was to determine the roles of Tregs in controlling type 2 inflammation and inhibiting eosinophilic infiltration in CRSwNP. A total of 134 nasal polyps, 67 ostiomeatal complex from chronic rhinosinusitis (CRS) and 62 normal nasal tissues from controls were collected to study the enumeration and function of Tregs cells and the expressions of cytokine profiles via immunofluorescence staining, flow cytometry, qRT-PCR, ELISA, and/or H&E staining. The effects of Tregs on type2 and type3 inflammations were determined in an eosinophilic chronic sinusitis (ECRS) mice model. It was confirmed that the CRSwNP displayed the features of Th2 and Th17 cells-mediated inflammation, accompanying by an increased level of eosinophilic infiltration and the eosinophil cationic protein (ECP), with a decreased frequency of Treg cells. Furthermore, the percentages of CD4+CD25+CD127lowTreg and CD4+CD25+Foxp3+Treg were only decreased in the polyps of CRSwNP but not in the paired peripheral blood. The CRSwNP possessed the decreased Nrp1+Tregs, Helios+Treg, and low TGF-β and interleukin (IL)-10 expressions in Tregs. The ECRS mice showed similar inflammatory characteristics to CRSwNP patients. The adoptive transfer of CD4+CD25+Foxp3+ Treg cells significantly decreased the inflammatory cytokines, eosinophilic chemotactic factors in the mucosa of the ECRS mice without alteration of the immune balance in the peripheral blood and spleen. In conclusion, CRSwNP showed high type 2 and type3 inflammation and defective Tregs. The induced regulatory T cell (iTreg) may correct the imbalance between immune tolerance and effect via limiting the eosinophil recruitment of mucosa in CRSwNP.
The TERT copy number gain is sensitive to telomerase inhibitors in human melanoma
Authors: Yu Jinyu , Yu Jiayi , Wu Xiaowen , Guo Qian , Yin Ting , Cheng Zhiyuan , Dai Jie , Kong Yan , Guo Jun 
Published: January 2020

Abstract
Telomerase reverse transcriptase (TERT) copy number gain is frequently observed in Asian melanoma patients. Here, we explored the correlation between TERT copy number and the effect of telomerase inhibitors in melanoma. A total of 78 melanoma cases were enrolled in the study. The TERT copy number was examined by QuantiGene Plex DNA assay. The sensitivity to telomerase inhibitors was evaluated in cell lines and patient-derived xenograft (PDX) models with or without TERT copy number gain. Among the 78 patients, 33.3% showed TERT copy number gain, and the incidence of this gain in acral melanoma (61.5%) was higher than that in other melanoma subtypes (P=0.02). The telomerase inhibitors 6-thio-2′-deoxyguanosine (6-Thio-dG) and epigallocatechin-3-gallate (EGCG) inhibited cell viability and repressed tumor growth in PDX models with TERT copy number gain. TERT copy number gain is frequently observed in Chinese patients with melanoma. Targeting telomerase may benefit melanoma patients with TERT copy number gain.
Acute myeloid leukemia immune escape by epigenetic CD48 silencing
Authors: Wang Zhiding , Xiao Yang , Guan Wei , Wang Mengzhen , Chen Jinghong , Zhang Linlin , Li Yan , Xiong Qian , Wang Hong , Wang Maoquan , Li Yuyan , Lv Na , Li Yonghui , Wang Lixin , Yu Li 
Published: January 2020

Abstract
Acute myeloid leukemia (AML) is a malignant disorder of hemopoietic stem cells. AML can escape immunosurveillance of natural killer (NK) by gene mutation, fusions and epigenetic modification. The mechanism of AML immune evasion is not clearly understood. Here we show that CD48 high expression is a favorable prognosis factor that is down-regulated in AML patients, which can help AML evade from NK cell recognition and killing. Furthermore, we demonstrate that CD48 expression is regulated by methylation and that a hypomethylating agent can increase the CD48 expression, which increases the NK cells killing in vitro. Finally, we show that CD48 high expression can reverse the AML immune evasion and activate NK cells function in vivo. The present study suggests that a combination the hypomethylating agent and NK cell infusion could be a new strategy to cure AML.
Shock acceleration efficiency in radio relics
Authors: Botteon A. , Brunetti G. , Ryu D. , Roh S. 
Published: January 2020

Context. Radio relics in galaxy clusters are giant diffuse synchrotron sources powered in cluster outskirts by merger shocks. Although the relic–shock connection has been consolidated in recent years by a number of observations, the details of the mechanisms leading to the formation of relativistic particles in this environment are still not well understood.
Aims. The diffusive shock acceleration (DSA) theory is a commonly adopted scenario to explain the origin of cosmic rays at astrophysical shocks, including those in radio relics in galaxy clusters. However, in a few specific cases it has been shown that the energy dissipated by cluster shocks is not enough to reproduce the luminosity of the relics via DSA of thermal particles. Studies based on samples of radio relics are required to further address this limitation of the mechanism.
Methods. In this paper, we focus on ten well-studied radio relics with underlying shocks observed in the X-rays and calculate the electron acceleration efficiency of these shocks that is necessary to reproduce the observed radio luminosity of the relics.
Results. We find that in general the standard DSA cannot explain the origin of the relics if electrons are accelerated from the thermal pool with an efficiency significantly smaller than 10%. Our results show that other mechanisms, such as shock re-acceleration of supra-thermal seed electrons or a modification of standard DSA, are required to explain the formation of radio relics.
The effect of drifts on the decay phase of SEP events
Authors: Wijsen N. , Aran A. , Sanahuja B. , Pomoell J. , Poedts S. 
Published: January 2020

Aims. We study the effect of the magnetic gradient and curvature drifts on the pitch-angle dependent transport of solar energetic particles (SEPs) in the heliosphere, focussing on ∼3–36 MeV protons. By considering observers located at different positions in the heliosphere, we investigate how drifts may alter the measured intensity-time profiles and energy spectra. We focus on the decay phase of solar energetic proton events in which a temporal invariant spectrum and disappearing spatial intensity gradients are often observed; a phenomenon known as the “reservoir effect” or the “SEP flood”. We study the effects of drifts by propagating particles both in nominal and non-nominal solar wind conditions.
Methods. We used a three-dimensional (3D) particle transport model, solving the focused transport equation extended with the effect of particle drifts in the spatial term. Nominal Parker solar wind configurations of different speeds and a magnetohydrodynamic (MHD) generated solar wind containing a corotating interaction region (CIR) were considered. The latter configuration gives rise to a magnetic bottle structure, with one bottleneck at the Sun and the other at the CIR. We inject protons from a fixed source at 0.1 AU, the inner boundary of the MHD model.
Results. When the drift induced particle net-flux is zero, the modelled intensity-time profiles obtained at different radial distances along an IMF line show the same intensity fall-off after the prompt phase of the particle event, which is in accordance with the SEP flood phenomenon. However, observers magnetically connected close to the edges of the particle injection site can experience, as a result of drifts, a sudden drop in the intensities occurring at different times for different energies such that no SEP flood phenomenon is established. In the magnetic bottle structure, this effect is enhanced due to the presence of magnetic field gradients strengthening the nominal particle drifts. Moreover, anisotropies can be large for observers that only receive particles through drifts, illustrating the importance of pitch-angle dependent 3D particle modelling. We observe that interplanetary cross-field diffusion can mitigate the effects of particle drifts.
Conclusions. Particle drifts can substantially modify the decay phase of SEP events, especially if the solar wind contains compression regions or shock waves where the drifts are enhanced. This is, for example, the case for our CIR solar wind configuration generated with a 3D MHD model, where the effect of drifts is strong. A similar decay rate in different energy channels and for different observers requires the mitigation of the effect of drifts. One way to accomplish this is through interplanetary cross-field diffusion, suggesting thus a way to determine a minimum value for the cross-field diffusion strength.
Building brand narratives with hashtags on Twitter
Authors: Pérez-Hernández Lorena 
Published: January 2020

AbstractThis paper investigates the use of hashtags in the building of brand narratives (i.e. the open-ended, unfolding and participative depiction of a company’s core ideology and beliefs). A collection of over 700 hashtags involved in the creation of the advertising narratives of the four leading soft drinks brands in 2017 (i.e.Coca-Cola, Pepsi, RedBull, Nescafé) has been analyzed both quantitatively and qualitatively to unveil their functions and formal characteristics, as well as the cognitive processes that underlie their interpretation and operate on the framing and dissemination of brand narratives. Ultimately, by categorizing and explaining the roles of hashtags in the construction of a brand narrative, as well as the potential correlations between their formal and functional traits and their retweeting rate and digital lifespan, this paper shapes a preliminary description of the characteristics of the subgenre of hashtag-based brand narratives and spells out some of the factors that should be considered in the choice of hashtags for advertising purposes.
genre as struggle
Authors: Tseng Ming-Yu 
Published: January 2020

Abstract
This study investigates the cognitive-pragmatic motivations for the emergence of a genre of health communication
called Patient Decision Aid (PDA). It elucidates genre as struggle, i.e. how the emerging genre
exemplifies various struggles on three strata: the difficulties facing patients, doctors, and health providers at practice level;
the changes anticipated to take place at discourse level; and the tensions in the pragmatics-cognition-society nexus. Particularly
illustrated here are five struggles that characterize changes or breakthroughs that PDAs are anticipated to make. It suggests that
the five struggles roughly correspond to five principles for genre theory proposed by Berkenkotter and Huckin (1993), with some modification of the latter. It also illustrates that genre intervenes in
the complexity between social issues and social cognition and that PDAs as a new genre involve restructuring, reshaping and
redesigning the key discourse facets (e.g. prior discourse, participants, language, medium, the world, and purpose). Based on
examples of Chinese-language PDAs officially released in Taiwan and on information from health professionals, policy makers, and
PDA developers, this study contributes empirical evidence toward a better understanding of an emerging genre.
Genre and constructional analysis
Authors: Nikiforidou Kiki 
Published: January 2020

AbstractConstructional approaches to genre model genre knowledge in terms of genre-based constructions. Like all constructions, these represent conventionalized pairings of meaning and form, of varying degrees of length and schematicity, whose pragmatic specifications include their association with a particular socio-cultural context. In this state-of-the-art article I review genre-related constructional work, discussing grammatical patterns that are licensed only in particular contexts, including conversational genres, as well as expressions that qualify as constructions simply on the basis of socio-cultural currency. The appropriateness of constructional analysis for the language of genre derives from the definitional incorporation of discourse-pragmatic information in constructional descriptions and the possibility of relating genre-bound, idiosyncratic patterns to the rest of the constructions in a language through relations of inheritance. I further highlight the compatibility of Frame Semantics with the notion of genre and critically discuss the concept of conventionality as it applies to genre language.
Genre as cognitive construction
Authors: Baicchi Annalisa , Iza Erviti Aneider 
Published: January 2020

AbstractThe present article investigates a set of discourse connectors in the academic lecture genre from the viewpoint of the inseparable pair of pragmatics and cognition. Making use of theMICASEcorpus for data retrieval, a selection of discourse constructions encoding comparative contrastive meanings are analysed and their distinctive features are critically described and explained. The aim is to show how each particular genre promotes the use of certain constructions. TheMICASEdatabase reveals that, among all the subgroups of complementary contrastive constructions, some seem incompatible with the academic lecture contexts by virtue of the particular characteristics of this specific genre.