bluuebunny/crossref_metadata_2025_split huggingface dataset:
p38-mediated phosphorylation at T367 induces EZH2 cytoplasmic localization to promote breast cancer metastasis
Authors: Anwar Talha , Arellano-Garcia Caroline , Ropa James , Chen Yu-Chih , Kim Hong Sun , Yoon Euisik , Grigsby Sierrah , Basrur Venkatesha , Nesvizhskii Alexey I. , Muntean Andrew , Gonzalez Maria E. , Kidwell Kelley M. , Nikolovska-Coleska Zaneta , Kleer Celina G. 
Published: July 2018

AbstractOverexpression of EZH2 in estrogen receptor negative (ER-) breast cancer promotes metastasis. EZH2 has been mainly studied as the catalytic component of the Polycomb Repressive Complex 2 (PRC2) that mediates gene repression by trimethylating histone H3 at lysine 27 (H3K27me3). However, how EZH2 drives metastasis despite the low H3K27me3 levels observed in ER- breast cancer is unknown. Here we show that in human invasive carcinomas and distant metastases, cytoplasmic EZH2 phosphorylated at T367 is significantly associated with ER- disease and low H3K27me3 levels. p38-mediated EZH2 phosphorylation at T367 promotes EZH2 cytoplasmic localization and potentiates EZH2 binding to vinculin and other cytoskeletal regulators of cell migration and invasion. Ectopic expression of a phospho-deficient T367A-EZH2 mutant is sufficient to inhibit EZH2 cytoplasmic expression, disrupt binding to cytoskeletal regulators, and reduce EZH2-mediated adhesion, migration, invasion, and development of spontaneous metastasis. These results point to a PRC2-independent non-canonical mechanism of EZH2 pro-metastatic function.
Propagation topography of redox phase transformations in heterogeneous layered oxide cathode materials
Authors: Mu Linqin , Yuan Qingxi , Tian Chixia , Wei Chenxi , Zhang Kai , Liu Jin , Pianetta Piero , Doeff Marca M. , Liu Yijin , Lin Feng 
Published: July 2018

AbstractRedox phase transformations are relevant to a number of metrics pertaining to the electrochemical performance of batteries. These phase transformations deviate from and are more complicated than the conventional theory of phase nucleation and propagation, owing to simultaneous changes of cationic and anionic valence states as well as the polycrystalline nature of battery materials. Herein, we propose an integrative approach of mapping valence states and constructing chemical topographies to investigate the redox phase transformation in polycrystalline layered oxide cathode materials under thermal abuse conditions. We discover that, in addition to the three-dimensional heterogeneous phase transformation, there is a mesoscale evolution of local valence curvatures in valence state topographies. The relative probability of negative and positive local valence curvatures alternates during the layered-to-spinel/rocksalt phase transformation. The implementation of our method can potentially provide a universal approach to study phase transformation behaviors in battery materials and beyond.
Nucleoporin 107, 62 and 153 mediate Kcnq1ot1 imprinted domain regulation in extraembryonic endoderm stem cells
Authors: Sachani Saqib S. , Landschoot Lauren S. , Zhang Liyue , White Carlee R. , MacDonald William A. , Golding Michael C. , Mann Mellissa R. W. 
Published: July 2018

AbstractGenomic imprinting is a phenomenon that restricts transcription to predominantly one parental allele. How this transcriptional duality is regulated is poorly understood. Here we perform an RNA interference screen for epigenetic factors involved in paternal allelic silencing at the Kcnq1ot1 imprinted domain in mouse extraembryonic endoderm stem cells. Multiple factors are identified, including nucleoporin 107 (NUP107). To determine NUP107’s role and specificity in Kcnq1ot1 imprinted domain regulation, we deplete Nup107, as well as Nup62, Nup98/96 and Nup153. Nup107, Nup62 and Nup153, but not Nup98/96 depletion, reduce Kcnq1ot1 noncoding RNA volume, displace the Kcnq1ot1 domain from the nuclear periphery, reactivate a subset of normally silent paternal alleles in the domain, alter histone modifications with concomitant changes in KMT2A, EZH2 and EHMT2 occupancy, as well as reduce cohesin interactions at the Kcnq1ot1 imprinting control region. Our results establish an important role for specific nucleoporins in mediating Kcnq1ot1 imprinted domain regulation.
Crystal structure of an L chain optimised 14F7 anti-ganglioside Fv suggests a unique tumour-specificity through an unusual H-chain CDR3 architecture
Authors: Bjerregaard-Andersen Kaare , Johannesen Hedda , Abdel-Rahman Noha , Heggelund Julie Elisabeth , Hoås Helene Mykland , Abraha Fana , Bousquet Paula A. , Høydahl Lene Støkken , Burschowsky Daniel , Rojas Gertrudis , Oscarson Stefan , Løset Geir Åge , Krengel Ute 
Published: July 2018

AbstractTargeted cancer immunotherapy offers increased efficacy concomitantly with reduced side effects. One antibody with promising clinical potential is 14F7, which specifically recognises the NeuGc GM3 ganglioside. This antigen is found in the plasma membrane of a range of tumours, but is essentially absent from healthy human cells. 14F7 can discriminate NeuGc GM3 from the very similar NeuAc GM3, a common component of cell membranes. The molecular basis for this unique specificity is poorly understood. Here we designed and expressed 14F7-derived single-chain Fvs (scFvs), which retained the specificity of the parent antibody. Detailed expression and purification protocols are described as well as the synthesis of the NeuGc GM3 trisaccharide. The most successful scFv construct, which comprises an alternative variable light chain (VLA), allowed structure determination to 2.2 Å resolution. The structure gives insights into the conformation of the important CDR H3 loop and the suspected antigen binding site. Furthermore, the presence of VLA instead of the original VL elucidates how this subdomain indirectly stabilises the CDR H3 loop. The current work may serve as a guideline for the efficient production of scFvs for structure determination.
Renoprotective effects of a factor Xa inhibitor: fusion of basic research and a database analysis
Authors: Horinouchi Yuya , Ikeda Yasumasa , Fukushima Keijo , Imanishi Masaki , Hamano Hirofumi , Izawa-Ishizawa Yuki , Zamami Yoshito , Takechi Kenshi , Miyamoto Licht , Fujino Hiromichi , Ishizawa Keisuke , Tsuchiya Koichiro , Tamaki Toshiaki 
Published: July 2018

AbstractRenal tubulointerstitial injury, an inflammation-associated condition, is a major cause of chronic kidney disease (CKD). Levels of activated factor X (FXa), a blood coagulation factor, are increased in various inflammatory diseases. Therefore, we investigated the protective effects of an FXa inhibitor against renal tubulointerstitial injury using unilateral ureteral obstruction (UUO) mice (a renal tubulointerstitial fibrosis model) and the Food and Drug Administration Adverse Events Reporting System (FAERS) database. The renal expression levels of FX and the FXa receptors protease-activated receptor (PAR)-1 and PAR-2 were significantly higher in UUO mice than in sham-operated mice. UUO-induced tubulointerstitial fibrosis and extracellular matrix expression were suppressed in UUO mice treated with the FXa inhibitor edoxaban. Additionally, edoxaban attenuated UUO-induced macrophage infiltration and inflammatory molecule upregulation. In an analysis of the FAERS database, there were significantly fewer reports of tubulointerstitial nephritis for patients treated with FXa inhibitors than for patients not treated with inhibitors. These results suggest that FXa inhibitors exert protective effects against CKD by inhibiting tubulointerstitial fibrosis.
Magnetic resonance as a local probe for kagomé magnetism in Barlowite Cu4(OH)6FBr
Authors: Ranjith K. M. , Klein C. , Tsirlin A. A. , Rosner H. , Krellner C. , Baenitz M. 
Published: July 2018

AbstractTemperature- and field-dependent 1H-, 19F-, and 79,81Br-NMR measurements together with zero - field 79,81Br-NQR measurements on polycrystalline samples of barlowite, Cu4(OH)6FBr are conducted to study the magnetism and possible structural distortions on a microscopic level. The temperature dependence of the 79,81Br-NMR spin-lattice relaxation rates 1/T1 indicate a phase transition at TN $$\simeq $$
≃
15 K which is of magnetic origin, but with an unusually weak slowing down of fluctuations below TN. Moreover, 1/T1T scales linear with the bulk susceptibility which indicates persisting spin fluctuations down to 2 K. Quadupolare resonance (NQR) studies reveal a pair of zero-field NQR- lines associated with the two isotopes of Br with the nuclear spins of I = 3/2. Quadrupole coupling constants of vQ ≃ 28.5 MHz and 24.7 MHz for 79Br- and 81Br-nuclei are determined from Br-NMR and the asymmetry parameter of the electric field gradient was estimated to η ≃ 0.2. The Br-NQR lines are consistent with our findings from Br-NMR and they are relatively broad, even above TN. This broadening and the relative large η value suggests a symmetry reduction at the Br- site reflecting the presence of a local distortion in the lattice. Our density-functional calculations show that the displacements of Cu2 atoms located between the kagome planes do not account for this relatively large η. On the other hand, full structural relaxation, including the deformation of kagome planes, leads to a better agreement with the experiment.
Association between Height and Actinic Keratosis: A Nationwide Population-based Study in South Korea
Authors: Lee Young Bok , Lee Ji Hyun , Kang Min Ji , Kim Jin-Wou , Yu Dong Soo , Han Kyung Do , Park Yong Gyu 
Published: July 2018

AbstractThe association between actinic keratosis (AK) and anthropometric measures has not been investigated. This study aims to evaluate the associations between anthropometric measures and the incidence of AK in South Korea. We analyzed clinical data from individuals aged over 20 years who received a health examination arranged by the national insurance program between 2005 and 2008. Newly diagnosed AK was identified using claims data from baseline to the date of diagnosis or until December 31, 2015. The incidence of AK was highest among the elderly (aged over 60 years) and showed a male bias. The risk of AK increased with greater height. The quintile with the greatest height had an increased risk of AK compared with the quintile with the lowest height (hazard ratio = 1.28, 95% confidence interval: 1.24–1.33) after adjustment for age, sex, income, smoking status, alcohol consumption, hypertension, dyslipidemia, myocardial infarction, congestive heart failure, and chronic obstructive pulmonary disease. This study showed a positive association between the incidence of AK and human height. However, it is unclear whether these findings can be generalized to Koreans who have not received an examination or to populations in other countries.
Assembly and Analysis of Unmapped Genome Sequence Reads Reveal Novel Sequence and Variation in Dogs
Authors: Holden Lindsay A. , Arumilli Meharji , Hytönen Marjo K. , Hundi Sruthi , Salojärvi Jarkko , Brown Kim H. , Lohi Hannes 
Published: July 2018

AbstractDogs are excellent animal models for human disease. They have extensive veterinary histories, pedigrees, and a unique genetic system due to breeding practices. Despite these advantages, one factor limiting their usefulness is the canine genome reference (CGR) which was assembled using a single purebred Boxer. Although a common practice, this results in many high-quality reads remaining unmapped. To address this whole-genome sequence data from three breeds, Border Collie (n = 26), Bearded Collie (n = 7), and Entlebucher Sennenhund (n = 8), were analyzed to identify novel, non-CGR genomic contigs using the previously validated pseudo-de novo assembly pipeline. We identified 256,957 novel contigs and paired-end relationships together with BLAT scores provided 126,555 (49%) high-quality contigs with genomic coordinates containing 4.6 Mb of novel sequence absent from the CGR. These contigs close 12,503 known gaps, including 2.4 Mb containing partially missing sequences for 11.5% of Ensembl, 16.4% of RefSeq and 12.2% of canFam3.1+ CGR annotated genes and 1,748 unmapped contigs containing 2,366 novel gene variants. Examples for six disease-associated genes (SCARF2, RD3, COL9A3, FAM161A, RASGRP1 and DLX6) containing gaps or alternate splice variants missing from the CGR are also presented. These findings from non-reference breeds support the need for improvement of the current Boxer-only CGR to avoid missing important biological information. The inclusion of the missing gene sequences into the CGR will facilitate identification of putative disease mutations across diverse breeds and phenotypes.
The trends of aquacultural nitrogen budget and its environmental implications in China
Authors: Luo Zhibo , Hu Shanying , Chen Dingjiang 
Published: July 2018

AbstractThe rapid development of aquaculture has sustained aquatic food production but has also led to a host of environmental problems, ranging from eutrophication of aquatic ecosystems to global acidification. China has become the world’s largest producer and consumer of aquaculture products. Nitrogen is an essential nutrient in aquaculture ecosystems, and the quantitative environmental fate and impact of nitrogen during aquaculture processes have notable environmental consequences but have received little attention. Here, we established a nitrogen cycling model for China’s aquaculture ecosystem to investigate the creation and fate of reactive nitrogen over a decadal time scale. A nitrogen balance analysis showed that reactive nitrogen input in the aquaculture ecosystem increased from 9.43 Tg N yr−1in 1978 to 18.54 Tg N yr−1in 2015, while aquaculture production increased from 0.034 to 1.33 Tg N yr−1during the same period. The environmental fate analysis showed that nitrogen emissions, accumulation, sediment deposition, and export into the oceans increased by 9.05-fold, 0.24-fold, 9.04-fold, and 2.56-fold, respectively. Finally, we investigated four scenarios representing different consumption levels of aquatic products and provided policy recommendations (larger aquaculture size, standardized aquaculture production model, nutritional element management and balanced dietary structure, etc.) on improved management practices in aquaculture ecosystems.
Immature particles and capsid-free viral RNA produced by Yellow fever virus-infected cells stimulate plasmacytoid dendritic cells to secrete interferons
Authors: Sinigaglia Laura , Gracias Ségolène , Décembre Elodie , Fritz Matthieu , Bruni Daniela , Smith Nikaïa , Herbeuval Jean-Philippe , Martin Annette , Dreux Marlène , Tangy Frédéric , Jouvenet Nolwenn 
Published: July 2018

AbstractPlasmacytoid dendritic cells (pDCs) are specialized in the production of interferons (IFNs) in response to viral infections. The Flaviviridae family comprises enveloped RNA viruses such as Hepatitis C virus (HCV) and Dengue virus (DENV). Cell-free flaviviridae virions poorly stimulate pDCs to produce IFN. By contrast, cells infected with HCV and DENV potently stimulate pDCs via short-range delivery of viral RNAs, which are either packaged within immature virions or secreted exosomes. We report that cells infected with Yellow fever virus (YFV), the prototypical flavivirus, stimulated pDCs to produce IFNs in a TLR7- and cell contact- dependent manner. Such stimulation was unaffected by the presence of YFV neutralizing antibodies. As reported for DENV, cells producing immature YFV particles were more potent at stimulating pDCs than cells releasing mature virions. Additionally, cells replicating a release-deficient YFV mutant or a YFV subgenomic RNA lacking structural protein-coding sequences participated in pDC stimulation. Thus, viral RNAs produced by YFV-infected cells reach pDCs via at least two mechanisms: within immature particles and as capsid-free RNAs. Our work highlights the ability of pDCs to respond to a variety of viral RNA-laden carriers generated from infected cells.
MDC1 methylation mediated by lysine methyltransferases EHMT1 and EHMT2 regulates active ATM accumulation flanking DNA damage sites
Authors: Watanabe Sugiko , Iimori Makoto , Chan David Virya , Hara Eiji , Kitao Hiroyuki , Maehara Yoshihiko 
Published: July 2018

AbstractChromatin dynamics mediated by post-translational modifications play a crucial role in cellular response to genotoxic stress for the maintenance of genome integrity. MDC1 is a pivotal chromatin adaptor in DNA damage response (DDR) and its methylation is essential to recruit repair factors at DNA double-strand break (DSB) sites, yet their precise molecular mechanisms remain elusive. Here we identified euchromatic histone-lysine N-methyltransferase 1 (EHMT1) and EHMT2 as novel regulators of MDC1, which is required for the accumulation of DDR factors e.g. 53BP1 and RAP80, at the DSB sites. MDC1 interacts mainly with EHMT1, which is facilitated by DNA damage-initiated ATM signalling, and EHMT2 dominantly modulates methylation of MDC1 lysine 45. This regulatory modification promotes the interaction between MDC1 and ATM to expand activated ATM on damaged chromatin and dysfunctional telomere. These findings identify EHMT1 and EHMT2 as DDR components, with implications for genome-integrity maintenance through proper dynamic methylation of MDC1.
Point-driven modern Chladni figures with symmetry breaking
Authors: Tuan P. H. , Lai Y. H. , Wen C. P. , Huang K. F. , Chen Y. F. 
Published: July 2018

AbstractPoint-driven modern Chladni figures subject to the symmetry breaking are systematically unveiled by developing a theoretical model and making experimental confirmation in the orthotropic brass. The plates with square shape are employed in the exploration based on the property that the orientation-dependent elastic anisotropy can be controlled by cutting the sides with a rotation angle with respect to the characteristic axes of the brass. Experimental results reveal that the orientation symmetry breaking not only causes the redistribution of resonant frequencies but also induces more resonant modes. More intriguingly, the driving position in some of new resonant modes can turn into the nodal point, whereas this position is always the anti-node in the isotropic case. The theoretical model is analytically developed by including a dimensionless parameter to consider the orientation symmetry-breaking effect in a generalized way. It is numerically verified that all experimental resonant frequencies and Chladni patterns can be well reconstructed with the developed model. The good agreement between theoretical calculations and experimental observations confirms the feasibility of using the developed model to analyze the modern Chladni experiment with orientation symmetry breaking. The developed model is believed to offer a powerful tool to build important database of plate resonant modes for the applications of controlling collective motions of micro objects.
Beeinflusst sportliche Aktivität die Revisionsrate nach Knietotalendoprothese? Analyse eines 12-Jahres-Follow-up
Authors: Valle Christina , Sperr Michael , Lemhöfer Christina , Bartel Karla , Schmitt-Sody Marcus 
Published: July 2018

Zusammenfassung
Hintergrund Der Anspruch von Patienten an Knietotalprothesen (KTEP) wächst zunehmend. Es stellt sich immer wieder die Frage, ob sportlich aktive Patienten nach Implantation einer KTEP ein erhöhtes Revisionsrisiko aufweisen im Vergleich zu Patienten ohne sportliche Aktivitäten.
Patienten/Material und Methoden In einer retrospektiven Studie wurden 130 Patienten mit einem Altersdurchschnitt von 69,2 Jahren zu Ihrer sportlichen Aktivität 22 Monate vor und nach KTEP Primärimplantation befragt. Die Patienten wurden aufgrund der Ergebnisse der Befragung in 2 Gruppen (A=Sport, B=No-Sport) eingeteilt. 7 Jahre postoperativ wurden dieselben Patienten erneut zu Ihrem Sportverhalten und 12 Jahre postoperativ zusätzlich zu stattgehabten Revisionsoperationen befragt.
Ergebnisse Von den 130 im Jahre 2005, ca. 2 Jahre nach KTEP-Implantation, befragten Patienten gaben 88 (67,7%) an, regelmäßig Sport auszuüben (Gruppe A) während 42 Patienten (32,3%) keinerlei Sport betrieben (Gruppe B). 2010 antworteten 87 der 130 Patienten auf die Befragung. 60 Patienten der Gruppe A waren weiterhin regelmäßig sportlich aktiv. 27 Patienten der Gruppe B gaben an, weiterhin keinerlei Sport zu betreiben. 2015 konnten von den 87 Patienten die 2010 befragt wurden immerhin noch 67 Patienten kontaktiert werden – davon 46 Patienten der Gruppe A und 21 Patienten der Gruppe B. In Gruppe A kam es 12 Jahre postoperative bei 7 von 46 Patienten (15,2%) zu Revisionsoperationen. In Gruppe B gaben 5 von 21 (23,8%) Patienten Revisionsoperationen im Sinne von Wechseloperationen in den letzten Jahren an.
Schlussfolgerung Es konnte gezeigt werden, dass 12 Jahre nach Primärimplantation einer KTEP die Revisionsrate in der Gruppe der sportlich aktiven Patienten verglichen mit den Inaktiven deutlich reduziert war. Daher lässt sich schlussfolgern, dass moderate sportliche Aktivität nach künstlichem Kniegelenkersatz keinen negativen Einfluss auf die Standzeit einer Knietotalendoprothese hat, sondern sogar möglicherweise zu verbesserter Osteointegration und damit zu weniger osteolytischen Reaktionen mit daraus resultierender aseptischer Prothesenlockerung führen könnte.
Editorial
Authors: Bantleon Hans-Peter , Schepp Niko 
Published: July 2018

Liebe Leserinnen und Leser,dieses Heft wurde von Niko Schepp in Kooperation mit den österreichischen Universitätszahnkliniken gestaltet. Die praktischen Aspekte der Kieferorthopädie beschreibt er als Praktiker in seinem Artikel über Nichtanlagen der zweiten Prämolaren im Unterkiefer anhand von 2 Fallberichten mit Lückenschluss. Weitere Fälle von Agenesien der seitlichen Schneidezähne werden von Jäger und Feldner abgehandelt.