bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gabbro-peridotite sills of the Late Riphean Dovyren plutonic complex (northern Baikal area, Russia)
Authors: Orsoev D.A. , Mekhonoshin A.S. , Kanakin S.V. , Badmatsyrenova R.A. , Khromova E.A. 
Published: May 2018

Abstract
We report data on the geology, mineralogy, petrography, and chemistry of 733 Ma gabbro-peridotite sills from the Late Riphean Dovyren plutonic complex. Thick sills were differentiated into plagiolherzolite to olivine gabbronorite compositions by fractional crystallization of the K–Na series high-Mg low-alkali low-Ti picritic parental magma. The magma already contained up to 5% of intratelluric olivine crystals when entering the reservoir. The sills emplaced before the whole complex, judging by the presence of their fragments as plagiolherzolite xenoliths in the gabbro zone of the Yoko-Dovyren layered pluton. The gabbro-peridotite sills are products of high-temperature within-plate magmatism. High heat flow during the generation of the magma, evident from its high-Mg composition, was likely maintained by the activity of a mantle plume associated with the Neoproterozoic Franklin large igneous province.
INTERSECTIONS OF MULTICURVES FROM DYNNIKOV COORDINATES
Authors: YURTTAŞ S. ÖYKÜ , HALL TOBY 
Published: May 2018

We present an algorithm for calculating the geometric intersection number of two multicurves on the$n$-punctured disk, taking as input their Dynnikov coordinates. The algorithm has complexity$O(m^{2}n^{4})$, where $m$is the sum of the absolute values of the Dynnikov coordinates of the two multicurves. The main ingredient is an algorithm due to Cumplido for relaxing a multicurve.
Workers and the Radical Right in Poland
Authors: Ost David 
Published: May 2018

AbstractHow has the Law and Justice Party in Poland (PiS) been able to get significant labor support to introduce far-right policies that undermine pluralist democracy? We look at PiS in the context of the “left fascist” traditions of the past, when redistributionist policies won wide support among workers who were accepted as part of the favored “nation.” Labor support breaks down along three lines, with industrial labor most closely aligned with PiS, white-collar labor (in education and health) mostly opposed, and the marginalized small-city precariat being mobilized by PiS, but also finding a place in explicitly fascist parties further to the Right. Left alternatives, weakened due to the collapse of class discourse, are slowly reemerging, but the Right will likely command most labor support for the near future.
“Italians First”: Workers on the Right Amidst Old and New Populisms
Authors: Zazzara Gilda 
Published: May 2018

AbstractThis article deals with the Italian working-class attitude to vote right-wing, seen in a long-term perspective, in particular in the northern and more industrialized regions. It stresses the fact that the left-wing parties reached their largest majority among working-class voters only for a short period. The end of the long cycle of factory conflicts of the 1970s on the one side, and the crisis of the “local political subcultures”—Catholic and Communist—in mediating the relationship between the working class and the central State on the other, marked the outbreak of a new political phenomenon: the establishment of the Lega Nord party in the 1980s. This party has been able to shift progressively from identity-based claims and secessionist proposals to xenophobia and the demand that a priority be accorded to Italian workers on the labour market. In the most recent years workers’ support for the Lega Nord has been contended by a new populist competitor, the Five Star Movement, whose ability to intercept a widespread “working-class malaise” will be tested in years to come.
Using Vertically Integrated Ocean Fields to Characterize Greenland Icebergs' Distribution and Lifetime
Authors: Marson Juliana M. , Myers Paul G. , Hu Xianmin , Le Sommer Julien 
Published: May 2018

AbstractIcebergs represent approximately half of Greenland's yearly mass loss, having important implications for biological productivity, freshwater fluxes in the ocean, and navigation. This study applies an iceberg model that uses integrated ocean fields (from surface to iceberg keel) to simulate the drift and decay of Greenland icebergs. This version of iceberg model (VERT) is compared with a more widely adopted version (SURF) which only uses surface ocean fields in its equations. We show that icebergs in VERT tend to drift along the shelf break, while in SURF they concentrate along the coastline. Additionally, we show that Greenland's southeast coast is the source of ∼60% of the icebergs that cross the interior of the Labrador Sea—a region that stages buoyancy‐driven convection and is, therefore, sensitive to freshwater input.
H I 21‐cm Cosmology and the Bispectrum: Closure Diagnostics in Massively Redundant Interferometric Arrays
Authors: Carilli C. L. , Nikolic Bojan , Thyagarajan Nithyanandan , Gale‐Sides K. 
Published: May 2018

AbstractNew, massively redundant low‐frequency arrays allow for a novel investigation of closure relations in interferometry. We employ commissioning data from the Hydrogen Epoch of Reionization Array to investigate closure quantities in this densely packed grid array of 14‐m antennas operating at 100 to 200 MHz. We investigate techniques that utilize closure phase spectra for redundant triads to estimate departures from redundancy for redundant baseline visibilities. We find a median absolute deviation from redundancy in closure phase across the observed frequency range of about 4.5°. This value translates into a nonredundancy per visibility phase of about 2.6°, using prototype electronics. The median absolute deviations from redundancy decrease with longer baselines. We show that closure phase spectra can be used to identify ill‐behaved antennas in the array, independent of calibration. We investigate the temporal behavior of closure spectra. The Allan variance increases after a 1‐min stride time, due to passage of the sky through the primary beam of the transit telescope. However, the closure spectra repeat to well within the noise per measurement at corresponding local sidereal times from day to day. In future papers in this series we will develop the technique of using closure phase spectra in the search for the H I 21‐cm signal from cosmic reionization.
IL-3 but not monomeric IgE regulates FcεRI levels and cell survival in primary human basophils
Authors: Zellweger Fabian , Buschor Patrick , Hobi Gabriel , Brigger Daniel , Dahinden Clemens Andreas , Villiger Peter Matthias , Eggel Alexander 
Published: May 2018

AbstractBinding of allergen-specific IgE to its primary receptor FcεRI on basophils and mast cells represents a central event in the development of allergic diseases. The high-affinity interaction between IgE and FcεRI results in permanent sensitization of these allergic effector cells and critically regulates their release of pro-inflammatory mediators upon IgE cross-linking by allergens. In addition, binding of monomeric IgE has been reported to actively regulate FcεRI surface levels and promote survival of mast cells in the absence of allergen through the induction of autocrine cytokine secretion including interleukin-3 (IL-3). As basophils and mast cells share many biological commonalities we sought to assess the role of monomeric IgE binding and IL-3 signaling in FcεRI regulation and cell survival of primary human basophils. FcεRI cell surface levels and survival of isolated blood basophils were assessed upon addition of monomeric IgE or physiologic removal of endogenous cell-bound IgE with a disruptive IgE inhibitor by flow cytometry. We further determined basophil cell numbers in both low and high serum IgE blood donors and mice that are either sufficient or deficient for FcεRI. Ultimately, we investigated the effect of IL-3 on basophil surface FcεRI levels by protein and gene expression analysis. Surface levels of FcεRI were passively stabilized but not actively upregulated in the presence of monomeric IgE. In contrast to previous observations with mast cells, monomeric IgE binding did not enhance basophil survival. Interestingly, we found that IL-3 transcriptionally regulates surface levels of FcεRI in human primary basophils. Our data suggest that IL-3 but not monomeric IgE regulates FcεRI expression and cell survival in primary human basophils. Thus, blocking of IL-3 signaling in allergic effector cells might represent an interesting approach to diminish surface FcεRI levels and to prevent prolonged cell survival in allergic inflammation.
HCC-derived exosomes elicit HCC progression and recurrence by epithelial-mesenchymal transition through MAPK/ERK signalling pathway
Authors: Chen Lu , Guo Piao , He Yuchao , Chen Ziye , Chen Liwei , Luo Yi , Qi Lisha , Liu Yuanyuan , Wu Qiang , Cui Yunlong , Fang Feng , Zhang Xiaofang , Song Tianqiang , Guo Hua 
Published: May 2018

AbstractLiver cancer is the second most common cause of cancer-related death worldwide. Approximately 70–90% of primary liver cancers are hepatocellular carcinoma (HCC). Currently, HCC patient prognosis is unsatisfactory due to high metastasis and/or post-surgical recurrence rates. Therefore, new therapeutic methods for inhibiting metastasis and recurrence are urgently needed. Exosomes are small lipid-bilayer vesicles that are implicated in tumour development and metastasis. Rab27a, a small GTPase, regulates exosome secretion by mediating multivesicular endosome docking at the plasma membrane. However, whether Rab27a participates in HCC cell-derived exosome exocytosis is unclear. Epithelial-mesenchymal transition (EMT) frequently initiates metastasis. The role of HCC cell-derived exosomes in EMT remains unknown. We found that exosomes from highly metastatic MHCC97H cells could communicate with low metastatic HCC cells, increasing their migration, chemotaxis and invasion. Rab27a knockdown inhibited MHCC97H-derived exosome secretion, which consequently promoted migration, chemotaxis and invasion in parental MHCC97H cells. Mechanistic studies showed that the biological alterations in HCC cells treated with MHCC97H-derived exosomes or MHCC97H cells with reduced self-derived exosome secretion were caused by inducing EMT via MAPK/ERK signalling. Animal experiments indicated that exosome secretion blockade was associated with enhanced lung and intrahepatic metastasis of parental MHCC97H cells, while ectopic overexpression of Rab27a in MHCC97H cells could rescue this enhancement of metastasis in vivo. Injection of MHCC97H cell-derived exosomes through the tail vein promoted intrahepatic recurrence of HLE tumours in vivo. Clinically, Rab27a was positively associated with serum alpha-fetoprotein (AFP) level, vascular invasion and liver cirrhosis. Our study elucidated the role of exosomes in HCC metastasis and recurrence, suggesting that they are promising therapeutic and prognostic targets for HCC patients.
BRD7 inhibits the Warburg effect and tumor progression through inactivation of HIF1α/LDHA axis in breast cancer
Authors: Niu Weihong , Luo Yanwei , Wang Xinye , Zhou Yao , Li Hui , Wang Heran , Fu Yaojie , Liu Shanshan , Yin Shanghelin , Li Jianglei , Zhao Ran , Liu Yukun , Fan Songqing , Li Zheng , Xiong Wei , Li Xiaoling , Li Guiyuan , Ren Caiping , Tan Ming , Zhou Ming 
Published: May 2018

AbstractThe bromodomain-containing protein 7 (BRD7) was first identified as a tumor suppressor in nasopharyngeal carcinoma and has critical roles in cancer development and progression. However, the regulatory roles and mechanisms of BRD7 in cancer metabolism are still unknown. In this study, we demonstrated that BRD7 was lowly expressed in breast cancer tissues and was identified as a poor prognostic factor in breast cancer. Meanwhile, BRD7 could suppress cell proliferation, initiate cell apoptosis and reduce aerobic glycolysis, suggesting that BRD7 plays a tumor suppressive roles in breast cancer. Mechanistically, BRD7 could negatively regulate a critical glycolytic enzyme LDHA through directly interaction with its upstream transcription factor, HIF1α, facilitating degradation of HIF1α mediated by ubiquitin–proteasome pathway. Moreover, restoring the expression of LDHA in breast cancer cells could reverse the effect of BRD7 on aerobic glycolysis, cell proliferation, and tumor formation, as well as the expression of cell cycle and apopotosis related molecules such as cyclin D1, CDK4, P21, and c-PARP both in vitro and in vivo. Taken together, these results indicate that BRD7 acts as a tumor suppressor in breast cancer and represses the glycolysis and tumor progression through inactivation of HIF1α/LDHA transcription axis.
MiR-422a regulates cellular metabolism and malignancy by targeting pyruvate dehydrogenase kinase 2 in gastric cancer
Authors: He Zhongyuan , Li Zheng , Zhang Xuan , Yin Kai , Wang Weizhi , Xu Zhipeng , Li Bowen , Zhang Lei , Xu Jianghao , Sun Guangli , Wang Lu , Li Qing , Huang Xiaoxu , Zhang Lu , Zhang Diancai , Xu Hao , Xu Zekuan 
Published: May 2018

AbstractIncreasing evidence indicates that dysregulation of microRNAs (miRNAs) plays a crucial role in human malignancies. Here, we showed that microRNA-422a (miR-422a) expression was dramatically downregulated in gastric cancer (GC) samples and cell lines compared with normal controls, and that its expression level was inversely related to tumor size and depth of infiltration. Functional studies revealed that the overexpression of miR-422a in GC tumor cells suppressed cell proliferation and migration, and drove a metabolic shift from aerobic glycolysis to oxidative phosphorylation. Mechanistic analysis suggested that miR-422a repressed pyruvate dehydrogenase kinase 2 (PDK2) to restore activity of the pyruvate dehydrogenase (PDH), the gatekeeping enzyme that catalyzes the decarboxylation of pyruvate to produce acetyl-CoA. Importantly, we further demonstrated that the mir-422a–PDK2 axis also influenced another metabolic pathway, de novo lipogenesis in cancer cells, and that it subsequently affected reactive oxygen species (ROS) and RB phosphorylation levels, ultimately resulting in cell cycle arrest in G1 phase. Our findings show that the miR-422a–PDK2 axis is an important mediator in metabolic reprogramming and a promising therapeutic target for antitumor treatment.
Femtosecond X-ray coherent diffraction of aligned amyloid fibrils on low background graphene
Authors: Seuring Carolin , Ayyer Kartik , Filippaki Eleftheria , Barthelmess Miriam , Longchamp Jean-Nicolas , Ringler Philippe , Pardini Tommaso , Wojtas David H. , Coleman Matthew A. , Dörner Katerina , Fuglerud Silje , Hammarin Greger , Habenstein Birgit , Langkilde Annette E. , Loquet Antoine , Meents Alke , Riek Roland , Stahlberg Henning , Boutet Sébastien , Hunter Mark S. , Koglin Jason , Liang Mengning , Ginn Helen M. , Millane Rick P. , Frank Matthias , Barty Anton , Chapman Henry N. 
Published: May 2018

AbstractHere we present a new approach to diffraction imaging of amyloid fibrils, combining a free-standing graphene support and single nanofocused X-ray pulses of femtosecond duration from an X-ray free-electron laser. Due to the very low background scattering from the graphene support and mutual alignment of filaments, diffraction from tobacco mosaic virus (TMV) filaments and amyloid protofibrils is obtained to 2.7 Å and 2.4 Å resolution in single diffraction patterns, respectively. Some TMV diffraction patterns exhibit asymmetry that indicates the presence of a limited number of axial rotations in the XFEL focus. Signal-to-noise levels from individual diffraction patterns are enhanced using computational alignment and merging, giving patterns that are superior to those obtainable from synchrotron radiation sources. We anticipate that our approach will be a starting point for further investigations into unsolved structures of filaments and other weakly scattering objects.
A comprehensive model for assessment of liver stage therapies targeting Plasmodium vivax and Plasmodium falciparum
Authors: Roth Alison , Maher Steven P. , Conway Amy J. , Ubalee Ratawan , Chaumeau Victor , Andolina Chiara , Kaba Stephen A. , Vantaux Amélie , Bakowski Malina A. , Thomson-Luque Richard , Adapa Swamy Rakesh , Singh Naresh , Barnes Samantha J. , Cooper Caitlin A. , Rouillier Mélanie , McNamara Case W. , Mikolajczak Sebastian A. , Sather Noah , Witkowski Benoît , Campo Brice , Kappe Stefan H. I. , Lanar David E. , Nosten François , Davidson Silas , Jiang Rays H. Y. , Kyle Dennis E. , Adams John H. 
Published: May 2018

AbstractMalaria liver stages represent an ideal therapeutic target with a bottleneck in parasite load and reduced clinical symptoms; however, current in vitro pre-erythrocytic (PE) models forPlasmodium vivaxandP.falciparumlack the efficiency necessary for rapid identification and effective evaluation of new vaccines and drugs, especially targeting late liver-stage development and hypnozoites. Herein we report the development of a 384-well plate culture system using commercially available materials, including cryopreserved primary human hepatocytes. Hepatocyte physiology is maintained for at least 30 days and supports development ofP.vivaxhypnozoites and complete maturation ofP.vivaxandP.falciparumschizonts. Our multimodal analysis in antimalarial therapeutic research identifies important PE inhibition mechanisms: immune antibodies against sporozoite surface proteins functionally inhibit liver stage development and ion homeostasis is essential for schizont and hypnozoite viability. This model can be implemented in laboratories in disease-endemic areas to accelerate vaccine and drug discovery research.
NOTCH-mediated non-cell autonomous regulation of chromatin structure during senescence
Authors: Parry Aled J. , Hoare Matthew , Bihary Dóra , Hänsel-Hertsch Robert , Smith Stephen , Tomimatsu Kosuke , Mannion Elizabeth , Smith Amy , D’Santos Paula , Russell I. Alasdair , Balasubramanian Shankar , Kimura Hiroshi , Samarajiwa Shamith A. , Narita Masashi 
Published: May 2018

AbstractSenescent cells interact with the surrounding microenvironment achieving diverse functional outcomes. We have recently identified that NOTCH1 can drive ‘lateral induction’ of a unique senescence phenotype in adjacent cells by specifically upregulating the NOTCH ligand JAG1. Here we show that NOTCH signalling can modulate chromatin structure autonomously and non-autonomously. In addition to senescence-associated heterochromatic foci (SAHF), oncogenic RAS-induced senescent (RIS) cells exhibit a massive increase in chromatin accessibility. NOTCH signalling suppresses SAHF and increased chromatin accessibility in this context. Strikingly, NOTCH-induced senescent cells, or cancer cells with high JAG1 expression, drive similar chromatin architectural changes in adjacent cells through cell–cell contact. Mechanistically, we show that NOTCH signalling represses the chromatin architectural protein HMGA1, an association found in multiple human cancers. Thus, HMGA1 is involved not only in SAHFs but also in RIS-driven chromatin accessibility. In conclusion, this study identifies that the JAG1–NOTCH–HMGA1 axis mediates the juxtacrine regulation of chromatin architecture.
Analysis of early changes in DNA methylation in synovial fibroblasts of RA patients before diagnosis
Authors: Karouzakis Emmanuel , Raza Karim , Kolling Christoph , Buckley Christopher D. , Gay Steffen , Filer Andrew , Ospelt Caroline 
Published: May 2018

AbstractDNA methylation is an important epigenetic modification that is known to be altered in rheumatoid arthritis synovial fibroblasts (RASF). Here, we compared the status of promoter DNA methylation of SF from patients with very early RA with SF from patients with resolving arthritis, fully established RA and from non-arthritic patients. DNA was hybridized to Infinium Human methylation 450k and 850k arrays and differential methylated genes and pathways were identified. We could identify a significant number of CpG sites that differed between the SF of different disease stages, showing that epigenetic changes in SF occur early in RA development. Principal component analysis confirmed that the different groups of SF were separated according to their DNA methylation state. Furthermore, pathway analysis showed that important functional pathways were altered in both very early and late RASF. By focusing our analysis on CpG sites in CpG islands within promoters, we identified genes that have significant hypermethylated promoters in very early RASF. Our data show that changes in DNA methylation differ in RASF compared to other forms of arthritis and occur at a very early, clinically yet unspecific stage of disease. The identified differential methylated genes might become valuable prognostic biomarkers for RA development.
Screen and Verification for Transgene Integration Sites in Pigs
Authors: Ma Linyuan , Wang Yuzhe , Wang Haitao , Hu Yiqing , Chen Jingyao , Tan Tan , Hu Man , Liu Xiaojuan , Zhang Ran , Xing Yiming , Zhao Yiqiang , Hu Xiaoxiang , Li Ning 
Published: May 2018

AbstractEfficient transgene expression in recipient cells constitutes the primary step in gene therapy. However, random integration in host genome comprises too many uncertainties. Our study presents a strategy combining bioinformatics and functional verification to find transgene integration sites in pig genome. Using an in silico approach, we screen out two candidate sites, namely, Pifs302 and Pifs501, located in actively transcribed intergenic regions with low nucleosome formation potential and without potential non-coding RNAs. After CRISPR/Cas9-mediated site-specific integration on Pifs501, we detected high EGFP expression in different pig cell types and ubiquitous EGFP expression in diverse tissues of transgenic pigs without adversely affecting 600 kb neighboring gene expression. Promoters integrated on Pifs501 exhibit hypomethylated modification, which suggest a permissive epigenetic status of this locus. We establish a versatile master cell line on Pifs501, which allows us to achieve site-specific exchange of EGFP to Follistatin with Cre/loxP system conveniently. Through in vitro and in vivo functional assays, we demonstrate the effectiveness of this screening method, and take Pifs501 as a potential site for transgene insertion in pigs. We anticipate that Pifs501 will have useful applications in pig genome engineering, though the identification of genomic safe harbor should over long-term various functional studies.
Genetic mapping identifies loci that influence tomato resistance against Colorado potato beetles
Authors: Vargas-Ortiz Erandi , Gonda Itay , Smeda John R. , Mutschler Martha A. , Giovannoni James J. , Jander Georg 
Published: May 2018

AbstractThe Colorado potato beetle (CPB; Leptinotarsa decemlineata Say), the most economically important insect pest on potato (Solanum tuberosum L.), also feeds on other Solanaceae, including cultivated tomato (Solanum lycopersicum L.). We used tomato genetic mapping populations to investigate natural variation in CPB resistance. CPB bioassays with 74 tomato lines carrying introgressions of Solanum pennellii in S. lycopersicum cv. M82 identified introgressions from S. pennellii on chromosomes 1 and 6 conferring CPB susceptibility, whereas introgressions on chromosomes 1, 8 and 10 conferred higher resistance. Mapping of CPB resistance using 113 recombinant inbred lines derived from a cross between S. lycopersicum cv UC-204B and Solanum galapagense identified significant quantitative trait loci on chromosomes 6 and 8. In each case, the S. galapagense alleles were associated with lower leaf damage and reduced larval growth. Results of both genetic mapping approaches converged on the same region of chromosome 6, which may have important functions in tomato defense against CPB herbivory. Although genetic mapping identified quantitative trait loci encompassing known genes for tomato acyl sugar and glycoalkaloid biosynthesis, experiments with acyl sugar near-isogenic lines and transgenic GAME9 glycoalkaloid-deficient and overproducing lines showed no significant effect of these otherwise insect-defensive metabolites on CPB performance.