bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of diterpenoid compounds that interfere with Fli-1 DNA binding to suppress leukemogenesis
Authors: Liu Tangjingjun , Xia Lei , Yao Yao , Yan Chen , Fan Yanhua , Gajendran Babu , Yang Jue , Li You-Jun , Chen Juan , Filmus Jorge , Spaner David E , Zacksenhaus Eldad , Hao Xiaojiang , Ben-David Yaacov 
Published: February 2019

AbstractThe ETS transcription factor Fli-1 controls the expression of genes involved in hematopoiesis including cell proliferation, survival, and differentiation. Dysregulation of Fli-1 induces hematopoietic and solid tumors, rendering it an important target for therapeutic intervention. Through high content screens of a library of chemicals isolated from medicinal plants in China for inhibitors of a Fli-1 transcriptional reporter cells, we hereby report the identification of diterpenoid-like compounds that strongly inhibit Fli-1 transcriptional activity. These agents suppressed the growth of erythroleukemic cells by inducing apoptosis and differentiation. They also inhibited survival and proliferation of B-cell leukemic cell lines as well as primary B-cell lymphocytic leukemia (B-CLL) isolated from 7 patients. Moreover, these inhibitors blocked leukemogenesis in a mouse model of erythroleukemia, in which Fli-1 is the driver of tumor initiation. Computational docking analysis revealed that the diterpenoid-like compounds bind with high affinity to nucleotide residues in a pocket near the major groove within the DNA-binding sites of Fli-1. Functional inhibition of Fli-1 by these compounds triggered its further downregulation through miR-145, whose promoter is normally repressed by Fli-1. These results uncover the importance of Fli-1 in leukemogenesis, a Fli-1-miR145 autoregulatory loop and new anti-Fli-1 diterpenoid agents for the treatment of diverse hematological malignancies overexpressing this transcription factor.
Obesity-associated inflammation triggers an autophagy–lysosomal response in adipocytes and causes degradation of perilipin 1
Authors: Ju Liping , Han Junfeng , Zhang Xiaoyan , Deng Yujie , Yan Han , Wang Congrong , Li Xiaohua , Chen Shuqin , Alimujiang Miriayi , Li Xu , Fang Qichen , Yang Ying , Jia Weiping 
Published: February 2019

AbstractIn obesity, adipocytes exhibit high metabolic activity accompanied by an increase in lipid mobilization. Recent findings indicate that autophagy plays an important role in metabolic homeostasis. However, the role of this process in adipocytes remains controversial. Therefore, we performed an overall analysis of the expression profiles of 322 lysosomal/autophagic genes in the omental adipose tissue of lean and obese individuals, and found that among 35 significantly differentially expressed genes, 34 genes were upregulated. A large number of lysosomal/autophagic genes also were upregulated in murine 3T3-L1 adipocytes challenged with tumor necrosis factor α (TNFα) (within 24 h), which is in accordance with increased autophagy flux in adipocytes. SQSTM1/p62, a selective autophagy receptor that recognizes and binds specifically to ubiquitinated proteins, is transcriptionally upregulated upon TNFα stimulation as well. Perilipin 1 (PLIN1), a crucial lipid droplet protein, can be ubiquitinated and interacts with SQSTM1 directly. Thus, TNFα-induced autophagy is a more selective process that signals through SQSTM1 and can selectively degrade PLIN1. Our study indicates that local proinflammatory cytokines in obese adipose tissue impair triglyceride storage via autophagy induction.
Selective photocatalytic conversion of methane into carbon monoxide over zinc-heteropolyacid-titania nanocomposites
Authors: Yu Xiang , De Waele Vincent , Löfberg Axel , Ordomsky Vitaly , Khodakov Andrei Y. 
Published: February 2019

AbstractChemical utilization of vast fossil and renewable feedstocks of methane remains one of the most important challenges of modern chemistry. Herein, we report direct and selective methane photocatalytic oxidation at ambient conditions into carbon monoxide, which is an important chemical intermediate and a platform molecule. The composite catalysts on the basis of zinc, tungstophosphoric acid and titania exhibit exceptional performance in this reaction, high carbon monoxide selectivity and quantum efficiency of 7.1% at 362 nm. In-situ Fourier transform infrared and X-ray photoelectron spectroscopy suggest that the catalytic performance can be attributed to zinc species highly dispersed on tungstophosphoric acid /titania, which undergo reduction and oxidation cycles during the reaction according to the Mars–van Krevelen sequence. The reaction proceeds via intermediate formation of surface methyl carbonates.
Reversible fold-switching controls the functional cycle of the antitermination factor RfaH
Authors: Zuber Philipp Konrad , Schweimer Kristian , Rösch Paul , Artsimovitch Irina , Knauer Stefan H. 
Published: February 2019

AbstractRfaH, member of the NusG/Spt5 family, activates virulence genes in Gram-negative pathogens. RfaH exists in two states, with its C-terminal domain (CTD) folded either as α-helical hairpin or β-barrel. In free RfaH, the α-helical CTD interacts with, and masks the RNA polymerase binding site on, the N-terminal domain, autoinhibiting RfaH and restricting its recruitment to opsDNA sequences. Upon activation, the domains separate and the CTD refolds into the β-barrel, which recruits a ribosome, activating translation. Using NMR spectroscopy, we show that only a complete ops-paused transcription elongation complex activates RfaH, probably via a transient encounter complex, allowing the refolded CTD to bind ribosomal protein S10. We also demonstrate that upon release from the elongation complex, the CTD transforms back into the autoinhibitory α-state, resetting the cycle. Transformation-coupled autoinhibition allows RfaH to achieve high specificity and potent activation of gene expression.
N-formyl-stabilizing quasi-catalytic species afford rapid and selective solvent-free amination of biomass-derived feedstocks
Authors: Li Hu , Guo Haixin , Su Yaqiong , Hiraga Yuya , Fang Zhen , Hensen Emiel J. M. , Watanabe Masaru , Smith Richard Lee 
Published: February 2019

AbstractNitrogen-containing compounds, especially primary amines, are vital building blocks in nature and industry. Herein, a protocol is developed that shows in situ formed N-formyl quasi-catalytic species afford highly selective synthesis of formamides or amines with controllable levels from a variety of aldehyde- and ketone-derived platform chemical substrates under solvent-free conditions. Up to 99% yields of mono-substituted formamides are obtained in 3 min. The C-N bond formation and N-formyl species are prevalent in the cascade reaction sequence. Kinetic and isotope labeling experiments explicitly demonstrate that the C-N bond is activated for subsequent hydrogenation, in which formic acid acts as acid catalyst, hydrogen donor and as N-formyl species source that stabilize amine intermediates elucidated with density functional theory. The protocol provides access to imides from aldehydes, ketones, carboxylic acids, and mixed-substrates, requires no special catalysts, solvents or techniques and provides new avenues for amination chemistry.
Hectd3 promotes pathogenic Th17 lineage through Stat3 activation and Malt1 signaling in neuroinflammation
Authors: Cho Jonathan J. , Xu Zhiwei , Parthasarathy Upasana , Drashansky Theodore T. , Helm Eric Y. , Zuniga Ashley N. , Lorentsen Kyle J. , Mansouri Samira , Cho Joshua Y. , Edelmann Mariola J. , Duong Duc M. , Gehring Torben , Seeholzer Thomas , Krappmann Daniel , Uddin Mohammad N. , Califano Danielle , Wang Rejean L. , Jin Lei , Li Hongmin , Lv Dongwen , Zhou Daohong , Zhou Liang , Avram Dorina 
Published: February 2019

AbstractPolyubiquitination promotes proteasomal degradation, or signaling and localization, of targeted proteins. Here we show that the E3 ubiquitin ligase Hectd3 is necessary for pathogenic Th17 cell generation in experimental autoimmune encephalomyelitis (EAE), a mouse model for human multiple sclerosis. Hectd3-deficient mice have lower EAE severity, reduced Th17 program and inefficient Th17 cell differentiation. However, Stat3, but not RORγt, has decreased polyubiquitination, as well as diminished tyrosine-705 activating phosphorylation. Additionally, non-degradative polyubiquitination of Malt1, critical for NF-κB activation and Th17 cell function, is reduced. Mechanistically, Hectd3 promotes K27-linked and K29-linked polyubiquitin chains on Malt1, and K27-linked polyubiquitin chains on Stat3. Moreover, Stat3 K180 and Malt1 K648 are targeted by Hectd3 for non-degradative polyubiquitination to mediate robust generation of RORγt+IL-17Ahi effector CD4+ T cells. Thus, our studies delineate a mechanism connecting signaling related polyubiquitination of Malt1 and Stat3, leading to NF-kB activation and RORγt expression, to pathogenic Th17 cell function in EAE.
Suppressed phase separation of mixed-halide perovskites confined in endotaxial matrices
Authors: Wang Xi , Ling Yichuan , Lian Xiujun , Xin Yan , Dhungana Kamal B. , Perez-Orive Fernando , Knox Javon , Chen Zhizhong , Zhou Yan , Beery Drake , Hanson Kenneth , Shi Jian , Lin Shangchao , Gao Hanwei 
Published: February 2019

AbstractThe functionality and performance of a semiconductor is determined by its bandgap. Alloying, as for instance in InxGa1-xN, has been a mainstream strategy for tuning the bandgap. Keeping the semiconductor alloys in the miscibility gap (being homogeneous), however, is non-trivial. This challenge is now being extended to halide perovskites – an emerging class of photovoltaic materials. While the bandgap can be conveniently tuned by mixing different halogen ions, as in CsPb(BrxI1-x)3, the so-called mixed-halide perovskites suffer from severe phase separation under illumination. Here, we discover that such phase separation can be highly suppressed by embedding nanocrystals of mixed-halide perovskites in an endotaxial matrix. The tuned bandgap remains remarkably stable under extremely intensive illumination. The agreement between the experiments and a nucleation model suggests that the size of the nanocrystals and the host-guest interfaces are critical for the photo-stability. The stabilized bandgap will be essential for the development of perovskite-based optoelectronics, such as tandem solar cells and full-color LEDs.
Japanese encephalitis virus neuropenetrance is driven by mast cell chymase
Authors: Hsieh Justin T. , Rathore Abhay P. S. , Soundarajan Gayathri , St. John Ashley L. 
Published: February 2019

AbstractJapanese encephalitis virus (JEV) is a leading cause of viral encephalitis. However, the mechanisms of JEV penetration of the blood-brain-barrier (BBB) remain poorly understood. Mast cells (MCs) are granulated innate immune sentinels located perivascularly, including at the BBB. Here we show that JEV activates MCs, leading to the release of granule-associated proteases in vivo. MC-deficient mice display reduced BBB permeability during JEV infection compared to congenic wild-type (WT) mice, indicating that enhanced vascular leakage in the brain during JEV infection is MC-dependent. Moreover, MCs promoted increased JEV infection in the central nervous system (CNS), enhanced neurological deficits, and reduced survival in vivo. Mechanistically, chymase, a MC-specific protease, enhances JEV-induced breakdown of the BBB and cleavage of tight-junction proteins. Chymase inhibition reversed BBB leakage, reduced brain infection and neurological deficits during JEV infection, and prolonged survival, suggesting chymase is a novel therapeutic target to prevent JEV encephalitis.
Electronic localization in CaVO3 films via bandwidth control
Authors: McNally Daniel E. , Lu Xingye , Pelliciari Jonathan , Beck Sophie , Dantz Marcus , Naamneh Muntaser , Shang Tian , Medarde Marisa , Schneider Christof W. , Strocov Vladimir N. , Pomjakushina Ekaterina V. , Ederer Claude , Radovic Milan , Schmitt Thorsten 
Published: February 2019

AbstractUnderstanding and controlling the electronic structure of thin layers of quantum materials is a crucial first step towards designing heterostructures where new phases and phenomena, including the metal-insulator transition (MIT), emerge. Here, we demonstrate control of the MIT via tuning electronic bandwidth and local site environment through selection of the number of atomic layers deposited. We take CaVO3, a correlated metal in its bulk form that has only a single electron in its V4+ 3d manifold, as a representative example. We find that thick films and ultrathin films (≤6 unit cells, u.c.) are metallic and insulating, respectively, while a 10 u.c. CaVO3 film exhibits a clear thermal MIT. Our combined X-ray absorption spectroscopy and resonant inelastic X-ray scattering (RIXS) study reveals that the thickness-induced MIT is triggered by electronic bandwidth reduction and local moment formation from V3+ ions, that are both a consequence of the thickness confinement. The thermal MIT in our 10 u.c. CaVO3 film exhibits similar changes in the RIXS response to that of the thickness-induced MIT in terms of reduction of bandwidth and V 3d–O 2p hybridization.
Enhanced germinal center reaction by targeting vaccine antigen to major histocompatibility complex class II molecules
Authors: Andersen Tor Kristian , Huszthy Peter C. , Gopalakrishnan Ramakrishna P. , Jacobsen Johanne T. , Fauskanger Marte , Tveita Anders A. , Grødeland Gunnveig , Bogen Bjarne 
Published: February 2019

AbstractEnhancing the germinal center (GC) reaction is a prime objective in vaccine development. Targeting of antigen to MHCII on APCs has previously been shown to increase antibody responses, but the underlying mechanism has been unclear. We have here investigated the GC reaction after targeting antigen to MHCII in (i) a defined model with T and B cells of known specificity using adjuvant-free vaccine proteins, and (ii) an infectious disease model using a DNA vaccine. MHCII-targeting enhanced presentation of peptide: MHCII on APCs, and increased the numbers of GC B cells, TFH, and plasma cells. Antibodies appeared earlier and levels were increased. BCR of GC B cells and serum antibodies had increased avidity for antigen. The improved responses required cross-linking of BCR and MHCII in eithercisortrans. The enhanced GC reaction induced by MHCII-targeting of antigen has clear implications for design of more efficient subunit vaccines.
A new genomic blueprint of the human gut microbiota
Authors: Almeida Alexandre , Mitchell Alex L. , Boland Miguel , Forster Samuel C. , Gloor Gregory B. , Tarkowska Aleksandra , Lawley Trevor D. , Finn Robert D. 
Published: February 2019

AbstractThe composition of the human gut microbiota is linked to health and disease, but knowledge of individual microbial species is needed to decipher their biological roles. Despite extensive culturing and sequencing efforts, the complete bacterial repertoire of the human gut microbiota remains undefined. Here we identify 1,952 uncultured candidate bacterial species by reconstructing 92,143 metagenome-assembled genomes from 11,850 human gut microbiomes. These uncultured genomes substantially expand the known species repertoire of the collective human gut microbiota, with a 281% increase in phylogenetic diversity. Although the newly identified species are less prevalent in well-studied populations compared to reference isolate genomes, they improve classification of understudied African and South American samples by more than 200%. These candidate species encode hundreds of newly identified biosynthetic gene clusters and possess a distinctive functional capacity that might explain their elusive nature. Our work expands the known diversity of uncultured gut bacteria, which provides unprecedented resolution for taxonomic and functional characterization of the intestinal microbiota.
Soluble TRAIL Armed Human MSC As Gene Therapy For Pancreatic Cancer
Authors: Spano Carlotta , Grisendi Giulia , Golinelli Giulia , Rossignoli Filippo , Prapa Malvina , Bestagno Marco , Candini Olivia , Petrachi Tiziana , Recchia Alessandra , Miselli Francesca , Rovesti Giulia , Orsi Giulia , Maiorana Antonino , Manni Paola , Veronesi Elena , Piccinno Maria Serena , Murgia Alba , Pinelli Massimo , Horwitz Edwin M. , Cascinu Stefano , Conte Pierfranco , Dominici Massimo 
Published: February 2019

AbstractPancreatic ductal adenocarcinoma (PDAC) is still one of the most aggressive adult cancers with an unacceptable prognosis. For this reason novel therapies accounting for PDAC peculiarities, such as the relevant stromal reaction, are urgently needed. Here adipose mesenchymal stromal/stem cells (AD-MSC) have been armed to constantly release a soluble trimeric and multimeric variant of the known anti-cancer TNF-related apoptosis-inducing ligand (sTRAIL). This cancer gene therapy strategy was in vitro challenged demonstrating that sTRAIL was thermally stable and able to induce apoptosis in the PDAC lines BxPC-3, MIA PaCa-2 and against primary PDAC cells. sTRAIL released by AD-MSC relocated into the tumor stroma was able to significantly counteract tumor growth in vivo with a significant reduction in tumor size, in cytokeratin-7+ cells and by an anti-angiogenic effect. In parallel, histology on PDAC specimens form patients (n = 19) was performed to investigate the levels of TRAIL DR4, DR5 and OPG receptors generating promising insights on the possible clinical translation of our approach. These results indicate that adipose MSC can very efficiently vehicle a novel TRAIL variant opening unexplored opportunities for PDAC treatment.
Live-cell imaging of subcellular structures for quantitative evaluation of pluripotent stem cells
Authors: Nishimura Ken , Ishiwata Hiroshi , Sakuragi Yuta , Hayashi Yohei , Fukuda Aya , Hisatake Koji 
Published: February 2019

AbstractPluripotent stem cells (PSCs) have various degrees of pluripotency, which necessitates selection of PSCs with high pluripotency before their application to regenerative medicine. However, the quality control processes for PSCs are costly and time-consuming, and it is essential to develop inexpensive and less laborious selection methods for translation of PSCs into clinical applications. Here we developed an imaging system, termed Phase Distribution (PD) imaging system, which visualizes subcellular structures quantitatively in unstained and unlabeled cells. The PD image and its derived PD index reflected the mitochondrial content, enabling quantitative evaluation of the degrees of somatic cell reprogramming and PSC differentiation. Moreover, the PD index allowed unbiased grouping of PSC colonies into those with high or low pluripotency without the aid of invasive methods. Finally, the PD imaging system produced three-dimensional images of PSC colonies, providing further criteria to evaluate pluripotency of PSCs. Thus, the PD imaging system may be utilized for screening of live PSCs with potentially high pluripotency prior to more rigorous quality control processes.
Synthesis of [18F]Favipiravir and Biodistribution in C3H/HeN Mice as Assessed by Positron Emission Tomography
Authors: Bocan Thomas M. , Basuli Falguni , Stafford Robert G. , Brown Jennifer L. , Zhang Xiang , Duplantier Allen J. , Swenson Rolf E. 
Published: February 2019

AbstractFavipiravir (T705; 6-fluoro-3-hydroxypyrazine-2-carboxamide) is a pyrazine analog that has demonstrated potent antiviral activity against a broad spectrum of viruses in multiple in vivo disease models. To better understand the compounds anti-viral activity, assessment of the drug’s biodistribution and kinetics in vivo may lend insight into how best to evaluate the compound efficacy preclinically and to contribute to the design of clinical studies to take into account the compound’s pharmacokinetic distribution and kinetics. In the current study, a method for synthesis of [18F]favipiravir was developed and the biodistribution in mice naïve to and pre-dosed with favipiravir was assessed by PET and gamma counting of tissue samples. Fluorine-18 labeling of favipiravir was achieved in a one-pot, two-step synthesis using a commercially available precursor, methyl-5-chloroisoxazolo[4,5-b]pyrazine-3-carboxylate, with an overall radiochemical yield of 15–24%, a molar activity of 37–74 GBq/µmol in a 70 minute synthesis time. [18F]favipiravir tissue uptake and distribution was similar in naïve and pre-dosed mice; however, in the pre-dosed animals plasma clearance was more rapid and tissue clearance appeared to be prolonged. In conclusion, application of PET to the evaluation of favipiravir has demonstrated the importance of dosing regimen on the distribution and tissue uptake and clearance of the molecule. Favipiravir is cleared through the kidney as previously reported but the liver and intestinal excretion may also play an important role in compound elimination. Measurement of the tissue uptake of favipiravir as determined by PET may be a more important indicator of a compound’s potential efficacy than purely monitoring plasma parameters such as viremia and drug levels.
Use of item response theory to develop a shortened version of the EORTC QLQ-BR23 scales
Authors: Xia Juan , Tang Zheng , Wu Peng , Wang Jiwei , Yu Jinming 
Published: February 2019

AbstractIt is important that questionnaires are as short as possible while still capturing the scope of problems relevant in an effective and reliable manner, to minimize the response burden. The purpose of our study was to develop a shortened version of the EORTC QLQ-BR23 for using in breast cancer survivors. Our data come from 10794 breast cancer survivors who completed the EORTC QLQ-BR23. Two-thirds of the sample was randomly selected from the original sample for development, and the remaining was used for validation. Item response theory methods were applied to shorten scales. The graded response model of Samejima was used to fit the item responses. The shortened scale was evaluated with the validation set by examining the mean difference, the proportion of respondents correctly predicted, correlation and weighted kappa between the shortened form and the original observed scores. Results reveal that a three-item BRBI, a four-item BRST, a three-item BRBS and a two-item BRAS forecast the scores on the original scales with wonderful consistency and are alike in measurement precision with no loss or only little loss in detecting group differences. Prospective validation on new diagnosed breast cancer patients and with poor QOL is needed.
Study of Optical Configurations for Multiple Enhancement of Microalgal Biomass Production
Authors: Cho Changsoon , Nam Kibok , Seo Yeong Hwan , Kim Kyoohyun , Park YongKeun , Han Jong-In , Lee Jung-Yong 
Published: February 2019

AbstractMicroalga is a promising biomass feedstock to restore the global carbon balance and produce sustainable bioenergy. However, the present biomass productivity of microalgae is not high enough to be marketable mainly because of the inefficient utilization of solar energy. Here, we study optical engineering strategies to lead to a breakthrough in the biomass productivity and photosynthesis efficiency of a microalgae cultivation system. Our innovative optical system modelling reveals the theoretical potential (>100 g m−2 day−1) of the biomass productivity and it is used to compare the optical aspects of various photobioreactor designs previously proposed. Based on the optical analysis, the optimized V-shaped configuration experimentally demonstrates an enhancement of biomass productivity from 20.7 m−2 day−1 to 52.0 g m−2 day−1, under the solar-simulating illumination of 7.2 kWh m−2 day−1, through the dilution and trapping of incident energy. The importance of quantitative optical study for microalgal photosynthesis is clearly exhibited with practical demonstration of the doubled light utilization efficiencies.