bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preventing inflammation inhibits biopsy-mediated changes in tumor cell behavior
Authors: Alieva Maria , Margarido Andreia S. , Wieles Tamara , Abels Erik R. , Colak Burcin , Boquetale Carla , Jan Noordmans Herke , Snijders Tom J. , Broekman Marike L. , van Rheenen Jacco 
Published: August 2017

AbstractAlthough biopsies and tumor resection are prognostically beneficial for glioblastomas (GBM), potential negative effects have also been suggested. Here, using retrospective study of patients and intravital imaging of mice, we identify some of these negative aspects, including stimulation of proliferation and migration of non-resected tumor cells, and provide a strategy to prevent these adverse effects. By repeated high-resolution intravital microscopy, we show that biopsy-like injury in GBM induces migration and proliferation of tumor cells through chemokine (C-C motif) ligand 2 (CCL-2)-dependent recruitment of macrophages. Blocking macrophage recruitment or administrating dexamethasone, a commonly used glucocorticoid to prevent brain edema in GBM patients, suppressed the observed inflammatory response and subsequent tumor growth upon biopsy both in mice and in multifocal GBM patients. Taken together, our study suggests that inhibiting CCL-2-dependent recruitment of macrophages may further increase the clinical benefits from surgical and biopsy procedures.
The FAD synthetase from the human pathogen Streptococcus pneumoniae: a bifunctional enzyme exhibiting activity-dependent redox requirements
Authors: Sebastián María , Lira-Navarrete Erandi , Serrano Ana , Marcuello Carlos , Velázquez-Campoy Adrián , Lostao Anabel , Hurtado-Guerrero Ramón , Medina Milagros , Martínez-Júlvez Marta 
Published: August 2017

AbstractProkaryotic bifunctional FAD synthetases (FADSs) catalyze the biosynthesis of FMN and FAD, whereas in eukaryotes two enzymes are required for the same purpose. FMN and FAD are key cofactors to maintain the flavoproteome homeostasis in all type of organisms. Here we shed light to the properties of the hitherto unstudied bacterial FADS from the human pathogen Streptococcus pneumoniae (SpnFADS). As other members of the family, SpnFADS catalyzes the three typical activities of prokaryotic FADSs: riboflavin kinase (RFK), ATP:FMN:adenylyltransferase (FMNAT), and FAD pyrophosphorylase (FADpp). However, several SpnFADS biophysical properties differ from those of other family members. In particular; i) the RFK activity is not inhibited by the riboflavin (RF) substrate, ii) the FMNAT and FADSpp activities require flavin substrates in the reduced state, iii) binding of adenine nucleotide ligands is required for the binding of flavinic substrates/products and iv) the monomer is the preferred state. Collectively, our results add interesting mechanistic differences among the few prokaryotic bifunctional FADSs already characterized, which might reflect the adaptation of the enzyme to relatively different environments. In a health point of view, differences among FADS family members provide us with a framework to design selective compounds targeting these enzymes for the treatment of diverse infectious diseases.
Whole transcriptome profiling of taste bud cells
Authors: Sukumaran Sunil K. , Lewandowski Brian C. , Qin Yumei , Kotha Ramana , Bachmanov Alexander A. , Margolskee Robert F. 
Published: August 2017

AbstractAnalysis of single-cell RNA-Seq data can provide insights into the specific functions of individual cell types that compose complex tissues. Here, we examined gene expression in two distinct subpopulations of mouse taste cells: Tas1r3-expressing type II cells and physiologically identified type III cells. Our RNA-Seq libraries met high quality control standards and accurately captured differential expression of marker genes for type II (e.g. the Tas1r genes, Plcb2, Trpm5) and type III (e.g. Pkd2l1, Ncam, Snap25) taste cells. Bioinformatics analysis showed that genes regulating responses to stimuli were up-regulated in type II cells, while pathways related to neuronal function were up-regulated in type III cells. We also identified highly expressed genes and pathways associated with chemotaxis and axon guidance, providing new insights into the mechanisms underlying integration of new taste cells into the taste bud. We validated our results by immunohistochemically confirming expression of selected genes encoding synaptic (Cplx2 and Pclo) and semaphorin signalling pathway (Crmp2, PlexinB1, Fes and Sema4a) components. The approach described here could provide a comprehensive map of gene expression for all taste cell subpopulations and will be particularly relevant for cell types in taste buds and other tissues that can be identified only by physiological methods.
Structural characterization of human Vaccinia-Related Kinases (VRK) bound to small-molecule inhibitors identifies different P-loop conformations
Authors: Couñago Rafael M. , Allerston Charles K. , Savitsky Pavel , Azevedo Hatylas , Godoi Paulo H. , Wells Carrow I. , Mascarello Alessandra , de Souza Gama Fernando H. , Massirer Katlin B. , Zuercher William J. , Guimarães Cristiano R. W. , Gileadi Opher 
Published: August 2017

AbstractThe human genome encodes two active Vaccinia-related protein kinases (VRK), VRK1 and VRK2. These proteins have been implicated in a number of cellular processes and linked to a variety of tumors. However, understanding the cellular role of VRKs and establishing their potential use as targets for therapeutic intervention has been limited by the lack of tool compounds that can specifically modulate the activity of these kinases in cells. Here we identified BI-D1870, a dihydropteridine inhibitor of RSK kinases, as a promising starting point for the development of chemical probes targeting the active VRKs. We solved co-crystal structures of both VRK1 and VRK2 bound to BI-D1870 and of VRK1 bound to two broad-spectrum inhibitors. These structures revealed that both VRKs can adopt a P-loop folded conformation, which is stabilized by different mechanisms on each protein. Based on these structures, we suggest modifications to the dihydropteridine scaffold that can be explored to produce potent and specific inhibitors towards VRK1 and VRK2.
Graphene nanoplatelets based matrix solid-phase dispersion microextraction for phenolic acids by ultrahigh performance liquid chromatography with electrochemical detection
Authors: Peng Li-Qing , Yi Ling , Yang Qiu-Cheng , Cao Jun , Du Li-Jing , Zhang Qi-Dong 
Published: August 2017

AbstractA simple, rapid and eco-friendly approach based on matrix solid-phase dispersion microextraction (MSPDM) followed by ultrahigh performance liquid chromatography coupled with electrochemical detection (UHPLC-ECD) was presented for the microextraction and determination of six phenolic acids in a plant preparation (Danshen tablets). The parameters that influenced the extraction performance of phenolic acids were investigated and optimized. The optimal MSPDM conditions were determined as follows: sorbent, using graphene nanoplatelets with sample/sorbent ratio of 1:1, grinding time set at 60 s, and 0.2 mL of water as elution solvent. Under the optimum conditions, the validation experiments indicated that the proposed method exhibited good linearity (r2 ≥ 0.9991), excellent precision (RSD ≤ 4.57%), and satisfactory recoveries (82.34–98.34%). The limits of detection were from 1.19 to 4.62 ng/mL for six phenolic acids. Compared with other reported methods, this proposal required less sample, solvent and extraction time. Consequently, the proposed method was successfully used to the extraction and determination of phenolic acids in Danshen tablets.
High sensitivity guided-mode-resonance optical sensor employing phase detection
Authors: Sahoo Pankaj K. , Sarkar Swagato , Joseph Joby 
Published: August 2017

AbstractWe report an ultra-sensitive refractive index (RI) sensor employing phase detection in a guided mode resonance (GMR) structure. By incorporating the GMR structure in to a Mach-Zehnder Interferometer, we measured the phase of GMR signal by calculating the amount of fringe shift. Since the phase of GMR signal varies rapidly around the resonance wavelength, the interference fringe pattern it forms with the reference signal becomes very sensitive to the surrounding RI change. The sensitivity comes out to be 0.608π phase shift per 10−4 RI change in water medium which is more than 100 times higher than the other reported GMR based phase detection method. In our setup, we can achieve a minimum phase shift of (1.94 × 10−3) π that corresponds to a RI change of 3.43 × 10−7, outperforming any of reported optical sensors and making it useful to detect RI changes in gaseous medium as well. We have developed a theoretical model to numerically estimate the phase shift of the GMR signal that predicts the experimental results very well. Our phase detection method comes out to be much more sensitive than the conventional GMR sensors based on wavelength or angle resolved scanning methods.
From Mechanistic Study to Chiral Catalyst Optimization: Theoretical Insight into Binaphthophosphepine-catalyzed Asymmetric Intramolecular [3 + 2] Cycloaddition
Authors: Duan Meng , Zhu Lei , Qi Xiaotian , Yu Zhaoyuan , Li Yingzi , Bai Ruopeng , Lan Yu 
Published: August 2017

AbstractDensity functional M11 was used to study the mechanism and enantioselectivity of a binaphthophosphepine-catalyzed intramolecular [3 + 2] cycloaddition reaction. The computational results revealed that this reaction proceeds through nucleophilic addition of the phosphine catalyst to the allene, which yields a zwitterionic phosphonium intermediate. The subsequent stepwise [3 + 2] annulation process, which starts with the intramolecular nucleophilic addition of the allenoate moiety to the electron-deficient olefin group, determines the enantioselectivity of the reaction. This step is followed by a ring-closing reaction and water-assisted proton-transfer process to afford the final product with concomitant regeneration of the phosphine catalyst. Theoretical predictions of the enantioselectivity for various phosphine catalysts were consistent with experimental observations, and 2D contour maps played an important role in explaining the origin of the enantioselectivity. Moreover, on the basis of our theoretical study, new binaphthophosphepine catalysts were designed and that are expecting to afford higher enantioselectivity in this cycloaddition reaction.
Long-range spontaneous droplet self-propulsion on wettability gradient surfaces
Authors: Liu Chaoran , Sun Jing , Li Jing , Xiang Chenghao , Che Lufeng , Wang Zuankai , Zhou Xiaofeng 
Published: August 2017

AbstractThe directional and long-range droplet transportation is of great importance in microfluidic systems. However, it usually requires external energy input. Here we designed a wettability gradient surface that can drive droplet motion by structural topography. The surface has a wettability gradient range of over 150° from superhydrophobic to hydrophilic, which was achieved by etching silicon nanopillars and adjusting the area of hydrophilic silicon dioxide plane. We conducted force analysis to further reveal the mechanism for droplet self-propulsion, and found that the nanostructures are critical to providing a large driving force and small resistance force. Theoretical calculation has been used to analyze the maximal self-propulsion displacement on different gradient surfaces with different volumes of droplets. On this basis, we designed several surfaces with arbitrary paths, which achieved directional and long-range transportation of droplet. These results clarify a driving mechanism for droplet self-propulsion on wettability gradient surfaces, and open up new opportunities for long-range and directional droplet transportation in microfluidic system.
CRISPR/Cas9-mediated genome editing efficiently creates specific mutations at multiple loci using one sgRNA in Brassica napus
Authors: Yang Hong , Wu Jia-Jing , Tang Ting , Liu Ke-De , Dai Cheng 
Published: August 2017

AbstractCRISPR/Cas9 is a valuable tool for both basic and applied research that has been widely applied to different plant species. Nonetheless, a systematical assessment of the efficiency of this method is not available for the allotetraploid Brassica napus—an important oilseed crop. In this study, we examined the mutation efficiency of the CRISPR/Cas9 method for 12 genes and also determined the pattern, specificity and heritability of these gene modifications in B. napus. The average mutation frequency for a single-gene targeted sgRNA in the T0 generation is 65.3%. For paralogous genes located in conserved regions that were targeted by sgRNAs, we observed mutation frequencies that ranged from 27.6% to 96.6%. Homozygotes were readily found in T0 plants. A total of 48.2% of the gene mutations, including homozygotes, bi-alleles, and heterozygotes were stably inherited as classic Mendelian alleles in the next generation (T1) without any new mutations or reversions. Moreover, no mutation was found in the putative off-target sites among the examined T0 plants. Collectively, our results demonstrate that CRISPR/Cas9 is an efficient tool for creating targeted genome modifications at multiple loci that are stable and inheritable in B. napus. These findings open many doors for biotechnological applications in oilseed crops.
Enhancing structural robustness of scale-free networks by information disturbance
Authors: Wu Jun , Tan Suo-Yi , Liu Zhong , Tan Yue-Jin , Lu Xin 
Published: August 2017

AbstractMany real-world systems can be described by scale-free networks with power-law degree distributions. Scale-free networks show a “robust yet fragile” feature due to their heterogeneous degree distributions. We propose to enhance the structural robustness of scale-free networks against intentional attacks by changing the displayed network structure information rather than modifying the network structure itself. We first introduce a simple mathematical model for attack information and investigate the impact of attack information on the structural robustness of scale-free networks. Both analytical and numerical results show that decreasing slightly the attack information perfection by information disturbance can dramatically enhance the structural robustness of scale-free networks. Then we propose an optimization model of disturbance strategies in which the cost constraint is considered. We analyze the optimal disturbance strategies and show an interesting but counterintuitive finding that disturbing “poor nodes” with low degrees preferentially is more effective than disturbing “rich nodes” with high degrees preferentially. We demonstrate the efficiency of our method by comparison with edge addition method and validate the feasibility of our method in two real-world critical infrastructure networks.
Nijmegen Breakage Syndrome fibroblasts and iPSCs: cellular models for uncovering disease-associated signaling pathways and establishing a screening platform for anti-oxidants
Authors: Mlody Barbara , Wruck Wasco , Martins Soraia , Sperling Karl , Adjaye James 
Published: August 2017

AbstractNijmegen Breakage Syndrome (NBS) is associated with cancer predisposition, premature aging, immune deficiency, microcephaly and is caused by mutations in the gene coding for NIBRIN (NBN) which is involved in DNA damage repair. Dermal-derived fibroblasts from NBS patients were reprogrammed into induced pluripotent stem cells (iPSCs) in order to bypass premature senescence. The influence of antioxidants on intracellular levels of ROS and DNA damage were screened and it was found that EDHB-an activator of the hypoxia pathway, decreased DNA damage in the presence of high oxidative stress. Furthermore, NBS fibroblasts but not NBS-iPSCs were found to be more susceptible to the induction of DNA damage than their healthy counterparts. Global transcriptome analysis comparing NBS to healthy fibroblasts and NBS-iPSCs to embryonic stem cells revealed regulation of P53 in NBS fibroblasts and NBS-iPSCs. Cell cycle related genes were down-regulated in NBS fibroblasts. Furthermore, oxidative phosphorylation was down-regulated and glycolysis up-regulated specifically in NBS-iPSCs compared to embryonic stem cells. Our study demonstrates the utility of NBS-iPSCs as a screening platform for anti-oxidants capable of suppressing DNA damage and a cellular model for studying NBN de-regulation in cancer and microcephaly.
Deterministic control of magnetic vortex wall chirality by electric field
Authors: Beardsley R. P. , Bowe S. , Parkes D. E. , Reardon C. , Edmonds K. W. , Gallagher B. L. , Cavill S. A. , Rushforth A. W. 
Published: August 2017

AbstractConcepts for information storage and logical processing based on magnetic domain walls have great potential for implementation in future information and communications technologies. To date, the need to apply power hungry magnetic fields or heat dissipating spin polarized currents to manipulate magnetic domain walls has limited the development of such technologies. The possibility of controlling magnetic domain walls using voltages offers an energy efficient route to overcome these limitations. Here we show that a voltage-induced uniaxial strain induces reversible deterministic switching of the chirality of a magnetic vortex wall. We discuss how this functionality will be applicable to schemes for information storage and logical processing, making a significant step towards the practical implementation of magnetic domain walls in energy efficient computing.
Seasonal changes in energy expenditure, body temperature and activity patterns in llamas (Lama glama)
Authors: Riek Alexander , Brinkmann Lea , Gauly Matthias , Perica Jurcevic , Ruf Thomas , Arnold Walter , Hambly Catherine , Speakman John R. , Gerken Martina 
Published: August 2017

AbstractMammals typically keep their body temperature (Tb) within a narrow limit with changing environmental conditions. There are indications that some wild ungulates can exhibit certain forms of energy saving mechanisms when ambient temperatures are low and/or food is scarce. Therefore, the aim of the study was to determine if the llama, one of the most extensively kept domestic livestock species, exhibits seasonal adjustment mechanisms in terms of energy expenditure, Tband locomotion. For that purpose llamas (N = 7) were kept in a temperate habitat on pasture. Locomotor activity, Tb(measured in the rumen) and the location of each animal were recorded continuously for one year using a telemetry system. Daily energy expenditure was measured as field metabolic rate (FMR). FMR fluctuated considerably between seasons with the lowest values found in winter (17.48 ± 3.98 MJ d−1, 402 kJ kg−0.75 d−1) and the highest in summer (25.87 ± 3.88 MJ d−1, 586 kJ kg−0.75 d−1). Llamas adjusted their energy expenditure, Tband locomotor activity according to season and also time of day. Thus, llamas seem to have maintained the ability to reduce their energy expenditure and adjust their Tbunder adverse environmental conditions as has been reported for some wild ungulates.
Anti-colon cancer effect of caffeic acid p-nitro-phenethyl ester in vitro and in vivo and detection of its metabolites
Authors: Tang Hao , Yao Xiaofang , Yao Cong , Zhao Xiaoyan , Zuo Hua , Li Zhubo 
Published: August 2017

AbstractCaffeic acid phenethyl ester (CAPE), extracted from propolis, was proven to inhibit colon cancer. Caffeic acid p-nitro-phenethyl ester (CAPE-pNO2), a derivative of CAPE, was determined to be an anti-platelet agent and a protector of myocardial ischaemia with more potent effects. In the present study, CAPE-pNO2 showed stronger cytotoxic activity than CAPE. We revealed interactions between CAPE-pNO2 and experimental cells. CAPE-pNO2 induced apoptosis in HT-29 cells by up-regulating P53, cleaved-caspase-3, Bax, P38 and CytoC; CAPE-pNO2 also up-regulated P21Cip1 and P27Kip1 and down-regulated CDK2 and c-Myc to promote cell cycle arrest in G0/G1. In xenograft studies, CAPE-pNO2 remarkably suppressed tumour growth dose dependently and decreased the expression of VEGF (vascular endothelial growth factor) in tumour tissue. Moreover, HE staining showed that no observable toxicity was found in the heart, liver, kidney and spleen. In addition, metabolites of CAPE-pNO2 in HT-29 cells and organs were detected. In conclusion, para-nitro may enhance the anticancer effect of CAPE by inhibiting colon cancer cell viability, inducing apoptosis and cell cycle arrest via the P53 pathway and inhibiting tumour growth and reducing tumour invasion by decreasing the expression of VEGF; additionally, metabolites of CAPE-pNO2 showed differences in cells and organs.
Early skeletal muscle loss during target therapy is a prognostic biomarker in metastatic renal cell carcinoma patients
Authors: Gu Weijie , Wu Junlong , Liu Xiaohang , Zhang Hailiang , Shi Guohai , Zhu Yao , Ye Dingwei 
Published: August 2017

AbstractSkeletal muscle depletion is common in patients with advanced cancer and may be associated with a poor outcome. To investigate whether the changes in skeletal muscle in metastatic renal cell carcinoma (mRCC) patients receiving targeted therapy are associated with clinical outcome, we undertook an observational cohort study using data from a number of randomized clinical trials previously conducted at the Fudan University Shanghai Cancer Center. The muscle mass was evaluated by comparing computed tomography images obtained at baseline with those obtained after 3–4 months of treatment. A total 101 patients were included in the study. The mean skeletal muscle area reduced from 41.6 cm2/m2 to 39.9 cm2/m2 after 3–4 months of targeted therapy. In multivariable analyses adjusted for the number of baseline covariates, muscle loss ≥5% was shown to be a significant prognostic factor for both progression-free (hazard ratio [HR]: 1.744, 95% confidence interval [CI]: 1.077–2.826, P = 0.024) and overall survival (HR: 2.367, 95%CI: 1.253–4.469, P = 0.008). The addition of muscle loss to the Heng model significantly improved its discriminative ability. In summary, early skeletal muscle loss is frequently observed in mRCC patients and can add prognostic information to current clinical risk scores.
Synthesis and structural studies of N-heterocyclic carbene Ag(I) and Hg(II) complexes and recognition of dihydrogen phosphate anion
Authors: Liu Qingxiang , Zhao Xiaoqiang , Hu Zeliang , Zhao Zhixiang , Wang Hong 
Published: August 2017

AbstractBis-benzimidazolium salt (S)-2,2′-bis[2″-(N-Et-benzimidazoliumyl)ethoxy]-1,1′-binaphthyl hexafluorophosphate [(S)-L1H2]·(PF6)2 and bis-imidazolium salts (S)-2,2′-bis[2″-(N-R-imidazoliumyl)ethoxy]-1,1′-binaphthyl hexafluorophosphate [(S)-L2H2]·(PF6)2 and [(S)-L3H2]·(PF6)2 (R = ethyl or benzyl), as well as their five N-heterocyclic carbene Hg(II) and Ag(I) complexes such as [(S)-L1Hg(HgBr4)] (1), [(S)-L2Hg(HgBr4)] (2), [(S)-L2Hg(HgI4)] (3), {[(S)-L2Ag](PF6)}n (4) and [(S)-L3Ag](PF6) (5) have been prepared and characterized. Each of complexes 1–3 consists of two rings (one 6-membered ring and one 11-membered ring), in which the oxygen atom in the ligand participates in coordination with Hg(II) ion. In complex 4, 1D helical polymeric chain is formed via biscarbene ligand (S)-L2 and Ag(I) ion. A 15-membered macrometallocycle is constructed through a ligand (S)-L3 and a Ag(I) ion in complex 5. Additionally, the selective recognition of H2PO4− using complex 5 as a receptor was investigated on the basis of fluorescence and UV/vis spectroscopic titrations. The results indicate that complex 5 can distinguish effectively H2PO4− from other anions.