bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel biomarkers for risk stratification of Barrett’s oesophagus associated neoplastic progression–epithelial HMGB1 expression and stromal lymphocytic phenotype
Authors: Porter Ross J. , Murray Graeme I. , Brice Daniel P. , Petty Russell D. , McLean Mairi H. 
Published: December 2019

Abstract
Background
The incidence of oesophageal adenocarcinoma is increasing globally. Barrett’s oesophagus (BO) is a pre-malignant condition with no biomarker to risk stratify those at highest risk of dysplasia and malignant transformation.

Methods
Subcellular epithelial protein (HMGB1, p53, RUNX3) expression, alongside expression of CD20, CD4, CD8 and Foxp3 to characterise stromal B lymphocyte, and helper, cytotoxic and regulatory T-lymphocyte cell infiltrate, respectively, was assessed by immunohistochemistry in 218 human tissue samples including normal oesophageal/gastric biopsies (n = 39), BO (non-dysplasia, dysplasia, non-dysplastic background from progressors to dysplasia or cancer, n = 121) and oesophageal adenocarcinoma (n = 58).

Results
There is a dynamic subcellular epithelial expression of HMGB1 (loss of nuclear, emergence of cytoplasmic), associated with epithelial p53 expression and differential immune cell phenotype in oesophageal neoplastic progression. We identify a protein signature and lymphocyte infiltrate in non-dysplastic BO when progressive disease (dysplasia or adenocarcinoma) is present but not histologically represented in the biopsied field. There is a dynamic stromal lymphocytic infiltrate in oesophageal neoplastic progression.

Conclusions
This data reveals novel insights into the microenvironment of BO and progression towards cancer and identifies a novel high-risk biomarker of disease progression to aid surveillance strategies to identify early progression and impact future incidence of oesophageal cancer.
Large Igneous Province thermogenic greenhouse gas flux could have initiated Paleocene-Eocene Thermal Maximum climate change
Authors: Jones Stephen M. , Hoggett Murray , Greene Sarah E. , Dunkley Jones Tom 
Published: December 2019

AbstractLarge Igneous Provinces (LIPs) are associated with the largest climate perturbations in Earth’s history. The North Atlantic Igneous Province (NAIP) and Paleocene-Eocene Thermal Maximum (PETM) constitute an exemplar of this association. As yet we have no means to reconstruct the pacing of LIP greenhouse gas emissions for comparison with climate records at millennial resolution. Here, we calculate carbon-based greenhouse gas fluxes associated with the NAIP at sub-millennial resolution by linking measurements of the mantle convection process that generated NAIP magma with observations of the individual geological structures that controlled gas emissions in a Monte Carlo framework. These simulations predict peak emissions flux of 0.2–0.5 PgC yr–1 and show that the NAIP could have initiated PETM climate change. This is the first predictive model of carbon emissions flux from any proposed PETM carbon source that is directly constrained by observations of the geological structures that controlled the emissions.
Probing the edge-related properties of atomically thin MoS2 at nanoscale
Authors: Huang Teng-Xiang , Cong Xin , Wu Si-Si , Lin Kai-Qiang , Yao Xu , He Yu-Han , Wu Jiang-Bin , Bao Yi-Fan , Huang Sheng-Chao , Wang Xiang , Tan Ping-Heng , Ren Bin 
Published: December 2019

AbstractDefects can induce drastic changes of the electronic properties of two-dimensional transition metal dichalcogenides and influence their applications. It is still a great challenge to characterize small defects and correlate their structures with properties. Here, we show that tip-enhanced Raman spectroscopy (TERS) can obtain distinctly different Raman features of edge defects in atomically thin MoS2, which allows us to probe their unique electronic properties and identify defect types (e.g., armchair and zigzag edges) in ambient. We observed an edge-induced Raman peak (396 cm−1) activated by the double resonance Raman scattering (DRRS) process and revealed electron–phonon interaction in edges. We further visualize the edge-induced band bending region by using this DRRS peak and electronic transition region using the electron density-sensitive Raman peak at 406 cm−1. The power of TERS demonstrated in MoS2 can also be extended to other 2D materials, which may guide the defect engineering for desired properties.
Diverse protein assembly driven by metal and chelating amino acids with selectivity and tunability
Authors: Yang Minwoo , Song Woon Ju 
Published: December 2019

AbstractProteins are versatile natural building blocks with highly complex and multifunctional architectures, and self-assembled protein structures have been created by the introduction of covalent, noncovalent, or metal-coordination bonding. Here, we report the robust, selective, and reversible metal coordination properties of unnatural chelating amino acids as the sufficient and dominant driving force for diverse protein self-assembly. Bipyridine-alanine is genetically incorporated into a D3 homohexamer. Depending on the position of the unnatural amino acid, 1-directional, crystalline and noncrystalline 2-directional, combinatory, and hierarchical architectures are effectively created upon the addition of metal ions. The length and shape of the structures is tunable by altering conditions related to thermodynamics and kinetics of metal-coordination and subsequent reactions. The crystalline 1-directional and 2-directional biomaterials retain their native enzymatic activities with increased thermal stability, suggesting that introducing chelating ligands provides a specific chemical basis to synthesize diverse protein-based functional materials while retaining their native structures and functions.
Metabolomics analysis of human acute graft-versus-host disease reveals changes in host and microbiota-derived metabolites
Authors: Michonneau David , Latis Eleonora , Curis Emmanuel , Dubouchet Laetitia , Ramamoorthy Sivapriya , Ingram Brian , de Latour Régis Peffault , Robin Marie , de Fontbrune Flore Sicre , Chevret Sylvie , Rogge Lars , Socié Gérard 
Published: December 2019

AbstractDespite improvement in clinical management, allogeneic hematopoietic stem cell transplantation (HSCT) is still hampered by high morbidity and mortality rates, mainly due to graft versus host disease (GvHD). Recently, it has been demonstrated that the allogeneic immune response might be influenced by external factors such as tissues microenvironment or host microbiota. Here we used high throughput metabolomics to analyze two cohorts of genotypically HLA-identical related recipient and donor pairs. Metabolomic profiles markedly differ between recipients and donors. At the onset of acute GvHD, in addition to host-derived metabolites, we identify significant variation in microbiota-derived metabolites, especially in aryl hydrocarbon receptor (AhR) ligands, bile acids and plasmalogens. Altogether, our findings support that the allogeneic immune response during acute GvHD might be influenced by bile acids and by the decreased production of AhR ligands by microbiota that could limit indoleamine 2,3-dioxygenase induction and influence allogeneic T cell reactivity.
Molecular insight into RNA polymerase I promoter recognition and promoter melting
Authors: Sadian Yashar , Baudin Florence , Tafur Lucas , Murciano Brice , Wetzel Rene , Weis Felix , Müller Christoph W. 
Published: December 2019

AbstractRNA polymerase I (Pol I) assembles with core factor (CF) and Rrn3 on the rDNA core promoter for transcription initiation. Here, we report cryo-EM structures of closed, intermediate and open Pol I initiation complexes from 2.7 to 3.7 Å resolution to visualize Pol I promoter melting and to structurally and biochemically characterize the recognition mechanism of Pol I promoter DNA. In the closed complex, double-stranded DNA runs outside the DNA-binding cleft. Rotation of CF and upstream DNA with respect to Pol I and Rrn3 results in the spontaneous loading and opening of the promoter followed by cleft closure and positioning of the Pol I A49 tandem winged helix domain (tWH) onto DNA. Conformational rearrangement of A49 tWH leads to a clash with Rrn3 to initiate complex disassembly and promoter escape. Comprehensive insight into the Pol I transcription initiation cycle allows comparisons with promoter opening by Pol II and Pol III.
Genomic and transcriptomic insights into molecular basis of sexually dimorphic nuptial spines in Leptobrachium leishanense
Authors: Li Jun , Yu Haiyan , Wang Wenxia , Fu Chao , Zhang Wei , Han Fengming , Wu Hua 
Published: December 2019

AbstractSexually dimorphic (SD) traits are important in sexual selection and species survival, yet the molecular basis remains elusive, especially in amphibians where SD traits have evolved repeatedly. We focus on the Leishan moustache toad (Leptobrachium leishanense), in which males develop nuptial spines on their maxillary skin. Here we report a 3.5 Gb genome assembly with a contig N50 of 1.93 Mb. We find a specific expansion of the intermediate filament gene family including numerous keratin genes. Within these genes, a cluster of duplicated hair keratin genes exhibits male-biased and maxillary skin-specific expression, suggesting a role in developing nuptial spines. We identify a module of coexpressed genes significantly associated with spine formation. In addition, we find several hormones likely to be involved in regulating spine development. This study not only presents a high-quality anuran genome but also provides a reference for studying skin-derived SD traits in amphibians.
Coherent electrical readout of defect spins in silicon carbide by photo-ionization at ambient conditions
Authors: Niethammer Matthias , Widmann Matthias , Rendler Torsten , Morioka Naoya , Chen Yu-Chen , Stöhr Rainer , Hassan Jawad Ul , Onoda Shinobu , Ohshima Takeshi , Lee Sang-Yun , Mukherjee Amlan , Isoya Junichi , Son Nguyen Tien , Wrachtrup Jörg 
Published: December 2019

AbstractQuantum technology relies on proper hardware, enabling coherent quantum state control as well as efficient quantum state readout. In this regard, wide-bandgap semiconductors are an emerging material platform with scalable wafer fabrication methods, hosting several promising spin-active point defects. Conventional readout protocols for defect spins rely on fluorescence detection and are limited by a low photon collection efficiency. Here, we demonstrate a photo-electrical detection technique for electron spins of silicon vacancy ensembles in the 4H polytype of silicon carbide (SiC). Further, we show coherent spin state control, proving that this electrical readout technique enables detection of coherent spin motion. Our readout works at ambient conditions, while other electrical readout approaches are often limited to low temperatures or high magnetic fields. Considering the excellent maturity of SiC electronics with the outstanding coherence properties of SiC defects, the approach presented here holds promises for scalability of future SiC quantum devices.
Cryo-EM structure of the human MLL1 core complex bound to the nucleosome
Authors: Park Sang Ho , Ayoub Alex , Lee Young-Tae , Xu Jing , Kim Hanseong , Zheng Wei , Zhang Biao , Sha Liang , An Sojin , Zhang Yang , Cianfrocco Michael A. , Su Min , Dou Yali , Cho Uhn-Soo 
Published: December 2019

AbstractMixed lineage leukemia (MLL) family histone methyltransferases are enzymes that deposit histone H3 Lys4 (K4) mono-/di-/tri-methylation and regulate gene expression in mammals. Despite extensive structural and biochemical studies, the molecular mechanisms whereby the MLL complexes recognize histone H3K4 within nucleosome core particles (NCPs) remain unclear. Here we report the single-particle cryo-electron microscopy (cryo-EM) structure of the NCP-bound human MLL1 core complex. We show that the MLL1 core complex anchors to the NCP via the conserved RbBP5 and ASH2L, which interact extensively with nucleosomal DNA and the surface close to the N-terminal tail of histone H4. Concurrent interactions of RbBP5 and ASH2L with the NCP uniquely align the catalytic MLL1SET domain at the nucleosome dyad, thereby facilitating symmetrical access to both H3K4 substrates within the NCP. Our study sheds light on how the MLL1 complex engages chromatin and how chromatin binding promotes MLL1 tri-methylation activity.
Examining multiple cellular pathways at once using multiplex hextuple luciferase assaying
Authors: Sarrion-Perdigones Alejandro , Chang Lyra , Gonzalez Yezabel , Gallego-Flores Tatiana , Young Damian W. , Venken Koen J. T. 
Published: December 2019

AbstractSensitive simultaneous assessment of multiple signaling pathways within the same cells requires orthogonal reporters that can assay over large dynamic ranges. Luciferases are such genetically encoded candidates due to their sensitivity, versatility, and cost-effectiveness. We expand luciferase multiplexing in post-lysis endpoint luciferase assays from two to six. Light emissions are distinguished by a combination of distinct substrates and emission spectra deconvolution. All six luciferase reporter units are stitched together into one plasmid facilitating delivery of all reporter units through a process we termed solotransfection, minimizing experimental errors. We engineer a multiplex hextuple luciferase assay to probe pathway fluxes through five transcriptional response elements against a control constitutive promoter. We can monitor effects of siRNA, ligand, and chemical compound treatments on their target pathways along with the four other probed cellular pathways. We demonstrate the effectiveness and adaptiveness of multiplex luciferase assaying, and its broad application across different research fields.
Reactivity mapping of nanoscale defect chemistry under electrochemical reaction conditions
Authors: Pfisterer Jonas H. K. , Baghernejad Masoud , Giuzio Giovanni , Domke Katrin F. 
Published: December 2019

AbstractElectrocatalysts often show increased conversion at nanoscale chemical or topographic surface inhomogeneities, resulting in spatially heterogeneous reactivity. Identifying reacting species locally with nanometer precision during chemical conversion is one of the biggest quests in electrochemical surface science to advance (electro)catalysis and related fields. Here, we demonstrate that electrochemical tip-enhanced Raman spectroscopy can be used for combined topography and reactivity imaging of electro-active surface sites under reaction conditions. We map the electrochemical oxidation of Au nanodefects, a showcase energy conversion and corrosion reaction, with a chemical spatial sensitivity of about 10 nm. The results indicate the reversible, concurrent formation of spatially separated Au2O3 and Au2O species at defect-terrace and protrusion sites on the defect, respectively. Active-site chemical nano-imaging under realistic working conditions is expected to be pivotal in a broad range of disciplines where quasi-atomistic reactivity understanding could enable strategic engineering of active sites to rationally tune (electro)chemical device properties.
Modulation of Indian monsoon by water vapor and cloud feedback over the past 22,000 years
Authors: Jalihal Chetankumar , Srinivasan Jayaraman , Chakraborty Arindam 
Published: December 2019

AbstractTo predict how monsoons will evolve in the 21st century, we need to understand how they have changed in the past. In paleoclimate literature, the major focus has been on the role of solar forcing on monsoons but not on the amplification by feedbacks internal to the climate system. Here we have used the results from a transient climate simulation to show that feedbacks amplify the effect of change in insolation on the Indian summer monsoon. We show that during the deglacial (22 ka to 10 ka) monsoons were predominantly influenced by rising water vapor due to increasing sea surface temperature, whereas in the Holocene (10 ka to 0 ka) cloud feedback was more important. These results are consistent with another transient simulation, thus increasing confidence despite potential model biases. We have demonstrated that insolation drives monsoon through different pathways during cold and warm periods, thereby highlighting the changing role of internal factors.
The small molecule inhibitor anle145c thermodynamically traps human islet amyloid peptide in the form of non-cytotoxic oligomers
Authors: Saravanan Manikam S. , Ryazanov Sergey , Leonov Andrei , Nicolai Janine , Praest Patrique , Giese Armin , Winter Roland , Khemtemourian Lucie , Griesinger Christian , Killian J. Antoinette 
Published: December 2019

AbstractType 2 diabetes (T2DM) is associated with aggregation of the human islet amyloid polypeptide (hIAPP) into cytotoxic amyloid species. Here we tested the effect of a diphenylpyrazole (DPP)-derived small molecule inhibitor, anle145c, on cytotoxicity and on aggregation properties of hIAPP. We demonstrate that incubation of hIAPP with the inhibitor yields ~10 nm-sized non-toxic oligomers, independent of the initial aggregation state of hIAPP. This suggests that anle145c has a special mode of action in which anle145c-stabilized oligomers act as a thermodynamic sink for the preferred aggregation state of hIAPP and anle145c. We also demonstrate that the inhibitor acts in a very efficient manner, with sub-stoichiometric concentrations of anle145c being sufficient to (i) inhibit hIAPP-induced death of INS-1E cells, (ii) prevent hIAPP fibril formation in solution, and (iii) convert preformed hIAPP fibrils into non-toxic oligomers. Together, these results indicate that anle145c is a promising candidate for inhibition of amyloid formation in T2DM.
A microemulsion high-performance liquid chromatography (MELC) method for the separation and determination of hydrolyzed tenuifolin in Radix Polygalae
Authors: Yan Hui , Zheng Zhuan-Di , Wu Hong-Fei , Liu Xiao-Chuang , Zhou An 
Published: December 2019

AbstractTenuifolin was used as a reliable chemical marker for the quality control of Radix Polygalae. The determination of tenuifolin is challenging because the analyte molecule lacks a suitable chromophore. The aim of this study was to establish a microemulsion high-performance liquid chromatography (MELC) method which is robust and sensitive, and can separate and determine tenuifolin in Radix Polygalae using an oil-in-water (O/W) microemulsion mobile phase. The separations were performed on a C18 (4.6 × 250 mm, 5 μm) column at 25 °C using a flow rate of 1.0 mL/min, and an ultraviolet detection wavelength of 210 nm. The microemulsion mobile phase comprised 2.8% (w/v) sodium dodecyl sulfate (SDS), 7.0% (v/v) n-butanol, 0.8% (v/v) n-octane and 0.1% (v/v) aqueous orthophosphate buffer (H3PO4). The linearity analysis of tenuifolin showed a correlation coefficient of 0.9923 in the concentration range of 48.00–960.00 µg/mL. The accuracy of the method based on three concentration levels ranged from 96.23% to 99.28%; the limit of detection (LOD) was 2.34 µg/mL, and the limit of quantification (LOQ) was 6.76 µg/mL. The results of our study indicated that the optimized MELC method was sensitive and robust, and can be widely applied for the separation and determination of tenuifolin in Radix Polygalae.
Immunomodulatory effect of Syphacia obvelata in treatment of experimental DSS-induced colitis in mouse model
Authors: Taghipour Niloofar , Mosaffa Nariman , Aghdaei Hamid Asadzadeh , Rostami-Nejad Mohammad , Weinstock Joel V. , Shahnavaz Sarira , Zali Mohammad Reza 
Published: December 2019

AbstractThe ability of helminth parasite infections to manipulate the immune system of their host towards T regulatory responses has been proposed to suppress the inflammatory response. The aim of this study was to investigate the protective and therapeutic effect of Syphacia obvelata in the treatment of experimental DSS -induced colitis. 50 male C57BL/6 mice were divided into 5 groups: healthy uninfected controls, DSS colitis, receiving only S. obv, preventive (S. obv + DSS) and therapeutic group (DSS + S.obv). Colitis intensity was investigated by measuring body weight changes, stool consistency/bleeding and colon length. To evaluate the immune responses induced by this nematode, TNF-α, IL-10, IL-17, IFN-γ and expressing of FoxP3+ T cells were measured in mesenteric lymph nodes and Peyer’s patches cells. Mice in preventive and therapeutic groups treated with S. obv egg significantly ameliorated the severity of the DSS colitis, indicated by the reduced disease manifestations, improved histopathological scores correlated with the up regulation of Treg responses and down regulation of proinflammatory cytokines. S. obv can prevention and reverse on-going murine DSS colitis. The data suggest that induction of Tregs and change in cytokine profiles during helminthic therapies were responsible for reversed inflammatory events in IBD.
Expression of XBP1s in peritoneal mesothelial cells is critical for inflammation-induced peritoneal fibrosis
Authors: Liu An , Song Qiong , Zheng Yong , Xu Guoshuang , Huang Chen , Sun Shiren , He Lijie , Zhao Lijuan , Zhou Meilan 
Published: December 2019

AbstractIntraperitoneal inflammation is the most important determinant of peritoneal fibrosis in patients with long-term peritoneal dialysis (PD). Spliced x-box binding protein-1 (XBP1s), a major proximal effector of unfolded protein response (UPR) signaling, plays an indispensable role in inflammation. Our study demonstrated that the inflammatory factor interleukin-1β (IL-1β) dose- and time-dependently induced XBP1s upregulation and interleukin-6 (IL-6) secretion, as well as the expression of the fibrotic marker fibronectin. However, these effects were prevented by the IRE1 endonuclease inhibitor STF083010 since it time-dependently reduced IL-1β-induced Xbp1 mRNA splicing, XBP1s protein expression, inflammatory factor IL-6 secretion and the expression of the fibrotic marker fibronectin in human peritoneal mesothelial cells (HPMCs). The overexpression and knockdown of XBP1s in HPMCs had a similar effect on fibronectin expression. In a rat model of peritoneal inflammation, STF083010 significantly attenuated chlorhexidine digluconate-induced XBP1s and α-smooth muscle actin expression, as well as fibrotic tissue proliferation, in the peritoneum. Our results suggest that XBP1s is a strong pathogenic factor that mediates inflammation-induced peritoneal fibrosis in peritoneal dialysis.
Altered microRNA and target gene expression related to Tetralogy of Fallot
Authors: Grunert Marcel , Appelt Sandra , Dunkel Ilona , Berger Felix , Sperling Silke R. 
Published: December 2019

AbstractMicroRNAs (miRNAs) play an important role in guiding development and maintaining function of the human heart. Dysregulation of miRNAs has been linked to various congenital heart diseases including Tetralogy of Fallot (TOF), which represents the most common cyanotic heart malformation in humans. Several studies have identified dysregulated miRNAs in right ventricular (RV) tissues of TOF patients. In this study, we profiled genome-wide the whole transcriptome and analyzed the relationship of miRNAs and mRNAs of RV tissues of a homogeneous group of 22 non-syndromic TOF patients. Observed profiles were compared to profiles obtained from right and left ventricular tissue of normal hearts. To reduce the commonly observed large list of predicted target genes of dysregulated miRNAs, we applied a stringent target prediction pipeline integrating probabilities for miRNA-mRNA interaction. The final list of disease-related miRNA-mRNA pairs comprises novel as well as known miRNAs including miR-1 and miR-133, which are essential to cardiac development and function by regulating KCNJ2, FBN2, SLC38A3 and TNNI1. Overall, our study provides additional insights into post-transcriptional gene regulation of malformed hearts of TOF patients.