bluuebunny/crossref_metadata_2025_split huggingface dataset:
The driver landscape of sporadic chordoma
Authors: Tarpey Patrick S. , Behjati Sam , Young Matthew D. , Martincorena Inigo , Alexandrov Ludmil B. , Farndon Sarah J. , Guzzo Charlotte , Hardy Claire , Latimer Calli , Butler Adam P. , Teague Jon W. , Shlien Adam , Futreal P. Andrew , Shah Sohrab , Bashashati Ali , Jamshidi Farzad , Nielsen Torsten O. , Huntsman David , Baumhoer Daniel , Brandner Sebastian , Wunder Jay , Dickson Brendan , Cogswell Patricia , Sommer Josh , Phillips Joanna J. , Amary M. Fernanda , Tirabosco Roberto , Pillay Nischalan , Yip Stephen , Stratton Michael R. , Flanagan Adrienne M. , Campbell Peter J. 
Published: October 2017

AbstractChordoma is a malignant, often incurable bone tumour showing notochordal differentiation. Here, we defined the somatic driver landscape of 104 cases of sporadic chordoma. We reveal somatic duplications of the notochordal transcription factor brachyury (T) in up to 27% of cases. These variants recapitulate the rearrangement architecture of the pathogenic germline duplications of T that underlie familial chordoma. In addition, we find potentially clinically actionable PI3K signalling mutations in 16% of cases. Intriguingly, one of the most frequently altered genes, mutated exclusively by inactivating mutation, was LYST (10%), which may represent a novel cancer gene in chordoma.
Single-molecule study of oxidative enzymatic deconstruction of cellulose
Authors: Eibinger Manuel , Sattelkow Jürgen , Ganner Thomas , Plank Harald , Nidetzky Bernd 
Published: October 2017

AbstractLPMO (lytic polysaccharide monooxygenase) represents a unique paradigm of cellulosic biomass degradation by an oxidative mechanism. Understanding the role of LPMO in deconstructing crystalline cellulose is fundamental to the enzyme’s biological function and will help to specify the use of LPMO in biorefinery applications. Here we show with real-time atomic force microscopy that C1 and C4 oxidizing types of LPMO from Neurospora crassa (NcLPMO9F, NcLPMO9C) bind to nanocrystalline cellulose with high preference for the very same substrate surfaces that are also used by a processive cellulase (Trichoderma reesei CBH I) to move along during hydrolytic cellulose degradation. The bound LPMOs, however, are immobile during their adsorbed residence time ( ~ 1.0 min for NcLPMO9F) on cellulose. Treatment with LPMO resulted in fibrillation of crystalline cellulose and strongly ( ≥ 2-fold) enhanced the cellulase adsorption. It also increased enzyme turnover on the cellulose surface, thus boosting the hydrolytic conversion.
EZH2 enables germinal centre formation through epigenetic silencing of CDKN1A and an Rb-E2F1 feedback loop
Authors: Béguelin Wendy , Rivas Martín A. , Calvo Fernández María T. , Teater Matt , Purwada Alberto , Redmond David , Shen Hao , Challman Matt F. , Elemento Olivier , Singh Ankur , Melnick Ari M. 
Published: October 2017

AbstractThe EZH2 histone methyltransferase is required for B cells to form germinal centers (GC). Here we show that EZH2 mediates GC formation through repression of cyclin-dependent kinase inhibitor CDKN1A (p21Cip1). Deletion of Cdkn1a rescues the GC reaction in Ezh2−/− mice. Using a 3D B cell follicular organoid system that mimics the GC reaction, we show that depletion of EZH2 suppresses G1 to S phase transition of GC B cells in a Cdkn1a-dependent manner. GC B cells of Cdkn1a−/−Ezh2−/− mice have high levels of phospho-Rb, indicating that loss of Cdkn1a enables progression of cell cycle. Moreover, the transcription factor E2F1 induces EZH2 during the GC reaction. E2f1−/− mice manifest impaired GC responses, which is rescued by restoring EZH2 expression, thus defining a positive feedback loop in which EZH2 controls GC B cell proliferation by suppressing CDKN1A, enabling cell cycle progression with a concomitant phosphorylation of Rb and release of E2F1.
Hollow MnO2 as a tumor-microenvironment-responsive biodegradable nano-platform for combination therapy favoring antitumor immune responses
Authors: Yang Guangbao , Xu Ligeng , Chao Yu , Xu Jun , Sun Xiaoqi , Wu Yifan , Peng Rui , Liu Zhuang 
Published: October 2017

AbstractHerein, an intelligent biodegradable hollow manganese dioxide (H-MnO2) nano-platform is developed for not only tumor microenvironment (TME)-specific imaging and on-demand drug release, but also modulation of hypoxic TME to enhance cancer therapy, resulting in comprehensive effects favoring anti-tumor immune responses. With hollow structures, H-MnO2 nanoshells post modification with polyethylene glycol (PEG) could be co-loaded with a photodynamic agent chlorine e6 (Ce6), and a chemotherapy drug doxorubicin (DOX). The obtained H-MnO2-PEG/C&D would be dissociated under reduced pH within TME to release loaded therapeutic molecules, and in the meantime induce decomposition of tumor endogenous H2O2 to relieve tumor hypoxia. As a result, a remarkable in vivo synergistic therapeutic effect is achieved through the combined chemo-photodynamic therapy, which simultaneously triggers a series of anti-tumor immune responses. Its further combination with checkpoint-blockade therapy would lead to inhibition of tumors at distant sites, promising for tumor metastasis treatment.
Dynamic regulation of canonical TGFβ signalling by endothelial transcription factor ERG protects from liver fibrogenesis
Authors: Dufton Neil P. , Peghaire Claire R. , Osuna-Almagro Lourdes , Raimondi Claudio , Kalna Viktoria , Chauhan Abhishek , Webb Gwilym , Yang Youwen , Birdsey Graeme M. , Lalor Patricia , Mason Justin C. , Adams David H. , Randi Anna M. 
Published: October 2017

AbstractThe role of the endothelium in protecting from chronic liver disease and TGFβ-mediated fibrosis remains unclear. Here we describe how the endothelial transcription factor ETS-related gene (ERG) promotes liver homoeostasis by controlling canonical TGFβ-SMAD signalling, driving the SMAD1 pathway while repressing SMAD3 activity. Molecular analysis shows that ERG binds to SMAD3, restricting its access to DNA. Ablation of ERG expression results in endothelial-to-mesenchymal transition (EndMT) and spontaneous liver fibrogenesis in EC-specific constitutive hemi-deficient (ErgcEC-Het) and inducible homozygous deficient mice (ErgiEC-KO), in a SMAD3-dependent manner. Acute administration of the TNF-α inhibitor etanercept inhibits carbon tetrachloride (CCL4)-induced fibrogenesis in an ERG-dependent manner in mice. Decreased ERG expression also correlates with EndMT in tissues from patients with end-stage liver fibrosis. These studies identify a pathogenic mechanism where loss of ERG causes endothelial-dependent liver fibrogenesis via regulation of SMAD2/3. Moreover, ERG represents a promising candidate biomarker for assessing EndMT in liver disease.
Phyllodes tumors with and without fibroadenoma-like areas display distinct genomic features and may evolve through distinct pathways
Authors: Pareja Fresia , Geyer Felipe C. , Kumar Rahul , Selenica Pier , Piscuoglio Salvatore , Ng Charlotte K. Y. , Burke Kathleen A. , Edelweiss Marcia , Murray Melissa P. , Brogi Edi , Weigelt Britta , Reis-Filho Jorge S. 
Published: October 2017

AbstractBreast fibroepithelial lesions (fibroadenomas and phyllodes tumors) are underpinned by recurrent MED12 exon 2 mutations, which are more common in fibroadenomas and benign phyllodes tumors. TERT promoter hotspot mutations have been documented in phyllodes tumors, and found to be more frequent in borderline and malignant lesions. Several lines of evidence suggest that a subset of phyllodes tumors might arise from fibroadenomas. Here we sought to investigate the genetic differences between phyllodes tumors with fibroadenoma-like areas vs. those without. We retrieved data for 16 borderline/ malignant phyllodes tumors, including seven phyllodes tumors with fibroadenoma-like areas and nine phyllodes tumors without fibroadenoma-like areas, which had been previously subjected to targeted capture massively parallel sequencing. Whilst MED12 exon 2 mutations were significantly more frequent in tumors with fibroadenoma-like areas (71 vs. 11%), an enrichment in genetic alterations targeting bona fide cancer genes was found in those without fibroadenoma-like areas, in particular in EGFR mutations and amplifications (78 vs. 14%). No significant difference in the frequency of TERT genetic alterations was observed (71% in cases with fibroadenoma-like areas vs 56% in those without fibroadenoma-like areas). Our data suggest that the development of phyllodes tumors might follow two different evolutionary pathways: a MED12-mutant pathway that involves the progression from a fibroadenoma to a malignant phyllodes tumor; and a MED12-wild-type pathway, where malignant phyllodes tumors arise de novo through the acquisition of genetic alterations targeting cancer genes. Additional studies are warranted to confirm our observations and define whether the outcome differs between both pathways.
The measurement of the surface energy of solids using a laboratory drop tower
Authors: Calvimontes Alfredo 
Published: October 2017

AbstractThis work presents a technique for the study and measurement of the interfacial energies of solid–liquid–gas systems. The instrument and the evaluation method for the measurements obtained by it, allow the analysis of the energy changes of sessile drops submitted to microgravity. A mathematical model based on the thermodynamic of wetting is applied to evaluate the interfacial energies as a function of the drop shape changes due to the effect of the release of gravitation during the experiment. The presented model bases on the thermodynamic equilibrium of the interfaces and not on the balance of bi-dimensional tensors on the contour line. For this reason, the model does not follow Young’s equation as the current surface wetting characterization techniques usually do.
Single-cell analysis of the fate of c-kit-positive bone marrow cells
Authors: Czarna Anna , Sanada Fumihiro , Matsuda Alex , Kim Junghyun , Signore Sergio , Pereira João D. , Sorrentino Andrea , Kannappan Ramaswamy , Cannatà Antonio , Hosoda Toru , Rota Marcello , Crea Filippo , Anversa Piero , Leri Annarosa 
Published: October 2017

AbstractThe plasticity of c-kit-positive bone marrow cells (c-kit-BMCs) in tissues different from their organ of origin remains unclear. We tested the hypothesis that c-kit-BMCs are functionally heterogeneous and only a subgroup of these cells possesses cardiomyogenic potential. Population-based assays fall short of identifying the properties of individual stem cells, imposing on us the introduction of single cell-based approaches to track the fate of c-kit-BMCs in the injured heart; they included viral gene-tagging, multicolor clonal-marking and transcriptional profiling. Based on these strategies, we report that single mouse c-kit-BMCs expand clonally within the infarcted myocardium and differentiate into specialized cardiac cells. Newly-formed cardiomyocytes, endothelial cells, fibroblasts and c-kit-BMCs showed in their genome common sites of viral integration, providing strong evidence in favor of the plasticity of a subset of BMCs expressing the c-kit receptor. Similarly, individual c-kit-BMCs, which were infected with multicolor reporters and injected in infarcted hearts, formed cardiomyocytes and vascular cells organized in clusters of similarly colored cells. The uniform distribution of fluorescent proteins in groups of specialized cells documented the polyclonal nature of myocardial regeneration. The transcriptional profile of myogenic c-kit-BMCs and whole c-kit-BMCs was defined by RNA sequencing. Genes relevant for engraftment, survival, migration, and differentiation were enriched in myogenic c-kit-BMCs, a cell subtype which could not be assigned to a specific hematopoietic lineage. Collectively, our findings demonstrate that the bone marrow comprises a category of cardiomyogenic, vasculogenic and/or fibrogenic c-kit-positive cells and a category of c-kit-positive cells that retains an undifferentiated state within the damaged heart.
Protective efficacy of a novel simian adenovirus vaccine against lethal MERS-CoV challenge in a transgenic human DPP4 mouse model
Authors: Munster Vincent J. , Wells Daniel , Lambe Teresa , Wright Daniel , Fischer Robert J. , Bushmaker Trenton , Saturday Greg , van Doremalen Neeltje , Gilbert Sarah C. , de Wit Emmie , Warimwe George M. 
Published: October 2017

AbstractMiddle East respiratory syndrome coronavirus (MERS-CoV) is a novel zoonotic virus that causes severe respiratory disease in humans with a case fatality rate close to 40%, but for which no vaccines are available. Here, we evaluated the utility of ChAdOx1, a promising replication-deficient simian adenovirus vaccine vector platform with an established safety profile in humans and dromedary camels, for MERS-CoV vaccine development. Using a transgenic lethal BALB/c MERS-CoV mouse model we showed that single dose intranasal or intramuscular immunisation with ChAdOx1 MERS, encoding full-length MERS-CoV Spike glycoprotein, is highly immunogenic and confers protection against lethal viral challenge. Immunogenicity and efficacy were comparable between immunisation routes. Together these data provide support for further evaluation of ChAdOx1 MERS vaccine in humans and dromedary camels, the animal reservoir of infection.
The Value of lncRNA NEAT1 as a Prognostic Factor for Survival of Cancer Outcome: A Meta-Analysis
Authors: Zhang Yunyuan , Lun Limin , Li Hui , Wang Qing , Lin Jieru , Tian Runhua , Pan Huazheng , Zhang Haiping , Chen Xian 
Published: October 2017

AbstractThe present meta-analysis aimed to analyze available data to identify the prognostic role of NEAT1 in multiple carcinomas. A systematic search was performed by using several computerized databases from inception to June 7, 2017. The quantity of the publications was assessed according to MOOSE checklist. Pooled HRs with 95% CI was calculated to summarize the effect. A total of 12 studies with 3,262 cancer patients were pooled in the analysis to evaluate the prognostic value of NEAT1 in multiple tumors. High expression levels of NEAT1 were demonstrated to be associated with poor OS (HR = 1.71, 95%CI: 1.37–2.14, P < 0.001) and tumor progression (III/IV vs. I/II: HR 1.76, 95%CI: 1.40–2.21, P < 0.00001). Subgroup analysis showed that NEAT1 detection method (qRT-PCR) and sample size (more or less than 100) did not alter the predictive value of NEAT1 on OS in various cancers. According to the meta-regression results, the large heterogeneity of meta-analysis may be attributed to the differences of NEAT1 detection method. Furthermore, elevated NEAT1 expression significantly predicted lymph node metastasis (HR: 2.10, 95%CI: 1.32–3.33, P = 0.002) and distant metastasis (HR: 2.80, 95%CI: 1.60–4.91, P = 0.0003) respectively. The results indicate that NEAT1 expression level is a prognostic biomarker for OS and metastasis in general tumors.
Observation of Contrary Thermo-responsive Trend for Single Crystal and Powder Samples in Mechano-, Thermo- and Solvato-responsive Luminescent Cubane [Ag4I4L4] Cluster
Authors: Li Shi-Li , Han Min , Wu Bin , Wang Jie , Zhang Fu-Qiang , Zhang Xian-Ming 
Published: October 2017

AbstractA new silver(I) iodide cluster [Ag4I4(TMP)4] (TMP = tris(3-methylphenyl)-phosphine) 1 shows triply stimuli-responsive luminescent chromism, namely, mechano-, thermo- and solvent-responsive chromism, which is isostructural to our previously reported [Cu4I4(TMP)4] 2 but shows quite different luminescence in response to the external stimuli. Especially, during the mechanical grinding, the relative intensities of HE and LE of 1 varied with a concomitant hypsochromic shift, and when the temperature was decreased from 300 to 5 K, unprecedented contrary thermo-responsive trend for single crystal and powered samples (blueshift of single crystals and redshift of powdered samples) was observed. These distinct characters of 1 should be due to the different molecular packing modes, metallic interactions and the unique character of Ag(I) ion.
HLA and Histo-Blood Group Antigen Expression in Human Pluripotent Stem Cells and their Derivatives
Authors: Säljö Karin , Barone Angela , Mölne Johan , Rydberg Lennart , Teneberg Susann , Breimer Michael E. 
Published: October 2017

AbstractOne prerequisite for a successful clinical outcome of human pluripotent stem cell (hPSC) based therapies is immune compatibility between grafted cells/tissue and recipient. This study explores immune determinants of human embryonic stem cell lines (hESC) and induced human pluripotent stem cell (hiPSC) lines and hepatocyte- and cardiomyocyte-like cells derived from these cells. HLA class I was expressed on all pluripotent hPSC lines which upon differentiation into hepatocyte-like cells was considerably reduced in contrast to cardiomyocyte-like cells which retained class I antigens. No HLA class II antigens were found in the pluripotent or differentiated cells. Histo-blood group carbohydrate antigens SSEA-3/SSEA-4/SSEA-5, Globo H, A, Lex/Ley and sialyl-lactotetra were expressed on all hPSC lines. Blood group AB(O)H antigen expression was in accordance with ABO genotype. Interestingly, only a subpopulation of A1O1 cells expressed A. During differentiation of hPSC, some histo-blood group antigens showed congruent alteration patterns while expression of other antigens differed between the cell lines. No systematic difference in the hPSC cell surface tissue antigen expression was detected. In conclusion, hPSC and their derivatives express cell surface antigens that may cause an immune rejection. Furthermore, tissue antigen expression must be established for each individual stem cell line prior to clinical application.
Crystal structure of the flexible tandem repeat domain of bacterial cellulose synthesis subunit C
Authors: Nojima Shingo , Fujishima Ayumi , Kato Koji , Ohuchi Kayoko , Shimizu Nobutaka , Yonezawa Kento , Tajima Kenji , Yao Min 
Published: October 2017

AbstractBacterial cellulose (BC) is synthesized and exported through the cell membrane via a large protein complex (terminal complex) that consists of three or four subunits. BcsC is a little-studied subunit considered to export BC to the extracellular matrix. It is predicted to have two domains: a tetratrico peptide repeat (TPR) domain and a β-barrelled outer membrane domain. Here we report the crystal structure of the N-terminal part of BcsC-TPR domain (Asp24–Arg272) derived from Enterobacter CJF-002. Unlike most TPR-containing proteins which have continuous TPR motifs, this structure has an extra α-helix between two clusters of TPR motifs. Five independent molecules in the crystal had three different conformations that varied at the hinge of the inserted α-helix. Such structural feature indicates that the inserted α-helix confers flexibility to the chain and changes the direction of the TPR super-helix, which was also suggested by structural analysis of BcsC-TPR (Asp24–Leu664) in solution by size exclusion chromatography-small-angle X-ray scattering. The flexibility at the α-helical hinge may play important role for exporting glucan chains.
Co-inoculum of Beauveria brongniartii and B. bassiana shows in vitro different metabolic behaviour in comparison to single inoculums
Authors: Canfora L. , Abu-Samra N. , Tartanus M. , Łabanowska B. H. , Benedetti A. , Pinzari F. , Malusà E. 
Published: October 2017

AbstractThe use of entomopathogenic fungi for biocontrol of plant pests is recently receiving an increased interest due to the need of reducing the impact of agricultural practices on the environment. Biocontrol efficacy could be improved by co-inoculation of different microorganisms. However, interactions between the fungal species can trigger or depress the biocontrol activity. Co-inoculation of two entomopathogenic fungi (Beauveria bassiana and B. brongniartii) was performed in vitro to evaluate the effects of their joint behaviour on a range of different carbon sources in comparison to single inoculation. The two species showed a very different metabolic profile by Phenotype MicroArrayTM. B. bassiana showed a broader metabolism than B. brongniartii on a range of substrates. B. brongniartii showed a greater specificity in substrate utilization. Several carbon sources (L-Asparagine, L-Aspartic Acid, L- Glutamic Acid, m- Erythritol, D-Melezitose, D-Sorbitol) triggered the fungal metabolism in the co-inoculum. SSR markers and Real Time qPCR analysis showed that different substrates promoted either the growth of one or the other species, suggesting a form of interaction between the two fungi, related to their different ecological niches. The methodological approach that combines Phenotype MicroArrayTM and SSR genotyping appeared useful to assess the performance and potential competition of co-inoculated entomopathogenic fungi.
Origins and transformations of dissolved organic matter in large Arctic rivers
Authors: Kaiser Karl , Canedo-Oropeza Maria , McMahon Rachel , Amon Rainer M. W. 
Published: October 2017

AbstractArctic river watersheds are important components of the global climate system and show an amplified response to climate change. Here, we characterize origins and transformations of dissolved organic matter (DOM) in five major Arctic rivers (Kolyma, Lena, Yenisei, Ob, Mackenzie) over 3 years with seasonal sampling periods using measurements of carbohydrates, amino acids, bacterial biomarkers (D-amino acids), and plant protein biomarkers (hydroxyproline). A strong seasonal cycle of bioavailable DOM export was observed that correlated with discharge, vegetation, river morphology and water residence time. The chemical composition of bioavailable DOM was different among rivers reflecting unique characteristics of Arctic river watersheds. Trends in specific bacterial biomarkers were synchronous to changes in bacterial community compositions demonstrating that bacterial communities responded to the seasonal shifts in organic matter quality and chemical composition. Extensive heterotrophic processing of plant and soil-derived DOM resulted in major inputs of bacterial detritus, and bacterial organic matter accounted for 21–42% of DOC in all watersheds. Dissolved organic nitrogen sources were dominated by bacterially-derived nitrogen and important contributions of soluble plant protein during the Spring freshet. Overall, our results demonstrated the importance of watershed characteristics and bacterial metabolism in regulating DOM composition, reactivity and carbon fluxes in Arctic river watersheds.
MCPH1, mutated in primary microcephaly, is required for efficient chromosome alignment during mitosis
Authors: Arroyo M. , Kuriyama R. , Trimborn M. , Keifenheim D. , Cañuelo A. , Sánchez A. , Clarke D. J. , Marchal J. A. 
Published: October 2017

AbstractMCPH1 gene, mutated in primary microcephaly, regulates cell progression into mitosis. While this role has been extensively investigated in the context of DNA damage, its function during unperturbed cell cycles has been given less attention. Here we have analyzed the dynamics of chromosome condensation and cell cycle progression in MCPH1 deficient cells under undamaging conditions. Our study demonstrates that chromosome condensation is uncoupled from cell cycle progression when MCPH1 function is lacking, resulting in cells that prematurely condense their chromosomes during mid G2-phase and delay decondensation at the completion of mitosis. However, mitosis onset occurs on schedule in MCPH1 deficient cells. We also revealed active Cdk1 to be mandatory for the premature onset of chromosome condensation during G2 and the maintenance of the condensed state thereafter. Interestingly, a novel cellular phenotype was observed while monitoring cell cycle progression in cells lacking MCPH1 function. Specifically, completion of chromosome alignment at the metaphase plate was significantly delayed. This deficiency reveals that MCPH1 is required for efficient chromosome biorientation during mitosis.