bluuebunny/crossref_metadata_2025_split huggingface dataset:
Upregulation of B7-H4 promotes tumor progression of intrahepatic cholangiocarcinoma
Authors: Xie Nan , Cai Jia-Bin , Zhang Lu , Zhang Peng-Fei , Shen Ying-Hao , Yang Xuan , Lu Jia-Cheng , Gao Dong-Mei , Kang Qiang , Liu Li-Xin , Zhang Chi , Huang Xiao-Yong , Zou Hao , Zhang Xin-Yu , Song Zheng-Ji , Sun Hai-Xiang , Fu Bi-Mang , Ke Ai-Wu , Shi Guo-Ming 
Published: December 2017

AbstractRecent reports show that B7-H4 is highly expressed in a variety of tumor cells, functions as a negative regulator of T cells and then promotes tumor progression. However, its expression and role in intrahepatic cholangiocarcinoma (ICC) remain unclear. In present study, B7-H4 expression in ICC and peritumoral tissues was determined at the level of mRNA and protein, and its bioactivity in ICC cells was studied after modification of B7-H4 expression. Then, the mechanism related to tumor progression induced by B7-H4 expression in ICC cells was explored. Finally, clinical significance of B7-H4 expression in ICC patients was further analyzed. The results showed that B7-H4 expression in ICC was much higher than that in peritumoral tissues at the level of both mRNA and protein. The high level of B7-H4 in ICC cells induced epithelial-to-mesenchymal transitions and promoted invasion and metastasis of tumor cells through activation of ERK1/2 signaling. The elevated B7-H4 expression was associated with the downregulated Bax, upregulated Bcl-2 expression, and activation of caspase-3. Clinically, high B7-H4 expression in tumor samples was significantly related to malignant phenotype, such as lymph node metastasis, high tumor stage, and poor differentiation. ICC patients with high expression of B7-H4 had shorter overall survival (OS) and disease-free survival. Moreover, the B7-H4 expression was an independent prognostic factor for predicting OS and tumor recurrence of ICC patients after operation. In conclusion, high expression of B7-H4 promotes tumor progression of ICC and may be a novel therapeutic target for ICC patients.
Experimental evidence supporting a global melt layer at the base of the Earth’s upper mantle
Authors: Freitas D. , Manthilake G. , Schiavi F. , Chantel J. , Bolfan-Casanova N. , Bouhifd M. A. , Andrault D. 
Published: December 2017

AbstractThe low-velocity layer (LVL) atop the 410-km discontinuity has been widely attributed to dehydration melting. In this study, we experimentally reproduced the wadsleyite-to-olivine phase transformation in the upwelling mantle across the 410-km discontinuity and investigated in situ the sound wave velocity during partial melting of hydrous peridotite. Our seismic velocity model indicates that the globally observed negative Vs anomaly (−4%) can be explained by a 0.7% melt fraction in peridotite at the base of the upper mantle. The produced melt is richer in FeO (~33 wt.%) and H2O (~16.5 wt.%) and its density is determined to be 3.56–3.74 g cm−3. The water content of this gravitationally stable melt in the LVL corresponds to a total water content in the mantle transition zone of 0.22 ± 0.02 wt.%. Such values agree with estimations based on magneto-telluric observations.
The evolutionary landscape of chronic lymphocytic leukemia treated with ibrutinib targeted therapy
Authors: Landau Dan A. , Sun Clare , Rosebrock Daniel , Herman Sarah E. M. , Fein Joshua , Sivina Mariela , Underbayev Chingiz , Liu Delong , Hoellenriegel Julia , Ravichandran Sarangan , Farooqui Mohammed Z. H. , Zhang Wandi , Cibulskis Carrie , Zviran Asaf , Neuberg Donna S. , Livitz Dimitri , Bozic Ivana , Leshchiner Ignaty , Getz Gad , Burger Jan A. , Wiestner Adrian , Wu Catherine J. 
Published: December 2017

AbstractTreatment of chronic lymphocytic leukemia (CLL) has shifted from chemo-immunotherapy to targeted agents. To define the evolutionary dynamics induced by targeted therapy in CLL, we perform serial exome and transcriptome sequencing for 61 ibrutinib-treated CLLs. Here, we report clonal shifts (change >0.1 in clonal cancer cell fraction, Q < 0.1) in 31% of patients during the first year of therapy, associated with adverse outcome. We also observe transcriptional downregulation of pathways mediating energy metabolism, cell cycle, and B cell receptor signaling. Known and previously undescribed mutations in BTK and PLCG2, or uncommonly, other candidate alterations are present in seventeen subjects at the time of progression. Thus, the frequently observed clonal shifts during the early treatment period and its potential association with adverse outcome may reflect greater evolutionary capacity, heralding the emergence of drug-resistant clones.
A hydrophobic anchor mechanism defines a deacetylase family that suppresses host response against YopJ effectors
Authors: Bürger Marco , Willige Björn C. , Chory Joanne 
Published: December 2017

AbstractSeveralPseudomonasandXanthomonasspecies are plant pathogens that infect the model organismArabidopsis thalianaand important crops such asBrassica. Resistant plants contain the infection by rapid cell death of the infected area through the hypersensitive response (HR). A family of highly related α/β hydrolases is involved in diverse processes in all domains of life. Functional details of their catalytic machinery, however, remained unclear. We report the crystal structures of α/β hydrolases representing two different clades of the family, including the protein SOBER1, which suppresses AvrBsT-incited HR inArabidopsis. Our results reveal a unique hydrophobic anchor mechanism that defines a previously unknown family of protein deacetylases. Furthermore, this study identifies a lid-loop as general feature for substrate turnover in acyl-protein thioesterases and the described family of deacetylases. Furthermore, we found that SOBER1’s biological function is not restricted toArabidopsis thalianaand not limited to suppress HR induced by AvrBsT.
Beneficial mutation-selection dynamics in finite asexual populations: a free boundary approach
Authors: Roques Lionel , Garnier Jimmy , Martin Guillaume 
Published: December 2017

AbstractUsing a free boundary approach based on an analogy with ice melting models, we propose a deterministic PDE framework to describe the dynamics of fitness distributions in the presence of beneficial mutations with non-epistatic effects on fitness. Contrarily to most approaches based on deterministic models, our framework does not rely on an infinite population size assumption, and successfully captures the transient as well as the long time dynamics of fitness distributions. In particular, consistently with stochastic individual-based approaches or stochastic PDE approaches, it leads to a constant asymptotic rate of adaptation at large times, that most deterministic approaches failed to describe. We derive analytic formulas for the asymptotic rate of adaptation and the full asymptotic distribution of fitness. These formulas depend explicitly on the population size, and are shown to be accurate for a wide range of population sizes and mutation rates, compared to individual-based simulations. Although we were not able to derive an analytic description for the transient dynamics, numerical computations lead to accurate predictions and are computationally efficient compared to stochastic simulations. These computations show that the fitness distribution converges towards a travelling wave with constant speed, and whose profile can be computed analytically.
A Micromagnetic Protocol for Qualitatively Predicting Stochastic Domain Wall Pinning
Authors: Omari K. A. , Hayward T. J. 
Published: December 2017

AbstractUnderstanding dynamically-induced stochastic switching effects in soft ferromagnetic nanowires is a critical challenge for realising spintronic devices with deterministic switching behaviour. Here, we present a micromagnetic simulation protocol for qualitatively predicting dynamic stochastic domain wall (DW) pinning/depinning at artificial defect sites in Ni80Fe20 nanowires, and demonstrate its abilities by correlating its predictions with the results of focused magneto-optic Kerr effect measurements. We analyse DW pinning configurations in both thin nanowires (t = 10 nm) and thick nanowires (t = 40 nm) with both single (asymmetric) and double (symmetric) notches, showing how our approach provides understanding of the complex DW-defect interactions at the heart of stochastic pinning behaviours. Key results explained by our model include the total suppression of stochastic pinning at single notches in thick nanowires and the intrinsic stochasticity of pinning at double notches, despite their apparent insensitivity to DW chirality.
Micro-patterned agarose gel devices for single-cell high-throughput microscopy of E. coli cells
Authors: Priest David G. , Tanaka Nobuyuki , Tanaka Yo , Taniguchi Yuichi 
Published: December 2017

AbstractHigh-throughput microscopy of bacterial cells elucidated fundamental cellular processes including cellular heterogeneity and cell division homeostasis. Polydimethylsiloxane (PDMS)-based microfluidic devices provide advantages including precise positioning of cells and throughput, however device fabrication is time-consuming and requires specialised skills. Agarose pads are a popular alternative, however cells often clump together, which hinders single cell quantitation. Here, we imprint agarose pads with micro-patterned ‘capsules’, to trap individual cells and ‘lines’, to direct cellular growth outwards in a straight line. We implement this micro-patterning into multi-pad devices called CapsuleHotel and LineHotel for high-throughput imaging. CapsuleHotel provides ~65,000 capsule structures per mm2 that isolate individual Escherichia coli cells. In contrast, LineHotel provides ~300 line structures per mm that direct growth of micro-colonies. With CapsuleHotel, a quantitative single cell dataset of ~10,000 cells across 24 samples can be acquired and analysed in under 1 hour. LineHotel allows tracking growth of > 10 micro-colonies across 24 samples simultaneously for up to 4 generations. These easy-to-use devices can be provided in kit format, and will accelerate discoveries in diverse fields ranging from microbiology to systems and synthetic biology.
Interaction of local solidification and remelting during dendrite coarsening - modeling and comparison with experiments
Authors: Zhang Qingyu , Fang Hui , Xue Hua , Pan Shiyan , Rettenmayr Markus , Zhu Mingfang 
Published: December 2017

AbstractThe microstructural evolution of dendrite coarsening during isothermal holding is simulated using a quantitative cellular automaton (CA) model involving the mechanisms of both solidification and melting. The present model encompasses the essential aspects of thermodynamics and kinetics, particularly the evolution/influence of composition, temperature, and curvature, leading to valid simulations of simultaneous solidification and melting. Model validation is performed through a comparison of the CA simulations with analytical predictions for a liquid pool migrating in the mushy zone of a SCN–0.3 wt.% ACE alloy due to temperature gradient zone melting. The model is applied to simulate the microstructural evolution of columnar dendrites of a SCN–2.0 wt.% ACE alloy during isothermal holding in a mushy zone. The simulation results are compared with those of a previous CA model that does not include the melting mechanism under otherwise identical conditions. The role of melting for dendrite coarsening is quantified, showing how the melting influences the coarsening process. The present model effectively reproduces the typical dendrite coarsening features as observed in experiments reported in the literature. The simulations reveal how local solidification and melting stimulate each other through the complicated interactions between phase transformation, interface shape variation, and solute diffusion.
Three-Dimensional Bi-Continuous Nanoporous Gold/Nickel Foam Supported MnO2 for High Performance Supercapacitors
Authors: Zhao Jie , Zou Xilai , Sun Peng , Cui Guofeng 
Published: December 2017

AbstractA three-dimensional bi-continuous nanoporous gold (NPG)/nickel foam is developed though the electrodeposition of a gold–tin alloy on Ni foam and subsequent chemical dealloying of tin. The newly-designed 3D metal structure is used to anchor MnO2nanosheets for high-performance supercapacitors. The formed ternary composite electrodes exhibit significantly-enhanced capacitance performance, rate capability, and excellent cycling stability. A specific capacitance of 442 Fg−1is achieved at a scan rate of 5 mV s−1and a relatively high mass loading of 865 μg cm−2. After 2500 cycles, only a 1% decay is found at a scan rate of 50 mV s−1. A high power density of 3513 W kg−1and an energy density of 25.73 Wh kg−1are realized for potential energy storage devices. The results demonstrate that the NPG/nickel foam hybrid structure significantly improves the dispersibility of MnO2and makes it promising for practical energy storage applications.
Ubiquitin Ligase Huwe1 Modulates Spermatogenesis by Regulating Spermatogonial Differentiation and Entry into Meiosis
Authors: Bose Rohini , Sheng Kai , Moawad Adel R. , Manku Gurpreet , O’Flaherty Cristian , Taketo Teruko , Culty Martine , Fok Kin Lam , Wing Simon S. 
Published: December 2017

AbstractSpermatogenesis consists of a series of highly regulated processes that include mitotic proliferation, meiosis and cellular remodeling. Although alterations in gene expression are well known to modulate spermatogenesis, posttranscriptional mechanisms are less well defined. The ubiquitin proteasome system plays a significant role in protein turnover and may be involved in these posttranscriptional mechanisms. We previously identified ubiquitin ligase Huwe1 in the testis and showed that it can ubiquitinate histones. Since modulation of histones is important at many steps in spermatogenesis, we performed a complete characterization of the functions of Huwe1 in this process by examining the effects of its inactivation in the differentiating spermatogonia, spermatocytes and spermatids. Inactivation of Huwe1 in differentiating spermatogonia led to their depletion and formation of fewer pre-leptotene spermatocytes. The cell degeneration was associated with an accumulation of DNA damage response protein γH2AX, impaired downstream signalling and apoptosis. Inactivation of Huwe1 in spermatocytes indicated that Huwe1 is not essential for meiosis and spermiogenesis, but can result in accumulation of γH2AX. Collectively, these results provide a comprehensive survey of the functions of Huwe1 in spermatogenesis and reveal Huwe1’s critical role as a modulator of the DNA damage response pathway in the earliest steps of spermatogonial differentiation.
Action of lytic polysaccharide monooxygenase on plant tissue is governed by cellular type
Authors: Chabbert Brigitte , Habrant Anouck , Herbaut Mickaël , Foulon Laurence , Aguié-Béghin Véronique , Garajova Sona , Grisel Sacha , Bennati-Granier Chloé , Gimbert-Herpoël Isabelle , Jamme Frédéric , Réfrégiers Matthieu , Sandt Christophe , Berrin Jean-Guy , Paës Gabriel 
Published: December 2017

AbstractLignocellulosic biomass bioconversion is hampered by the structural and chemical complexity of the network created by cellulose, hemicellulose and lignin. Biological conversion of lignocellulose involves synergistic action of a large array of enzymes including the recently discovered lytic polysaccharide monooxygenases (LPMOs) that perform oxidative cleavage of cellulose. Using in situ imaging by synchrotron UV fluorescence, we have shown that the addition of AA9 LPMO (from Podospora anserina) to cellulases cocktail improves the progression of enzymes in delignified Miscanthus x giganteus as observed at tissular levels. In situ chemical monitoring of cell wall modifications performed by synchrotron infrared spectroscopy during enzymatic hydrolysis demonstrated that the boosting effect of the AA9 LPMO was dependent on the cellular type indicating contrasted recalcitrance levels in plant tissues. Our study provides a useful strategy for investigating enzyme dynamics and activity in plant cell wall to improve enzymatic cocktails aimed at expanding lignocelluloses biorefinery.
Gastrectomy compared to oesophagectomy for Siewert II and III gastro-oesophageal junctional cancer in relation to resection margins, lymphadenectomy and survival
Authors: Kauppila Joonas H. , Wahlin Karl , Lagergren Jesper 
Published: December 2017

AbstractIt is unclear whether gastrectomy or oesophagectomy offer better outcomes for gastro-oesophageal junction (GOJ) cancer. A total of 240 patients undergoing total gastrectomy (n = 85) or oesophagectomy (n = 155) for Siewert II-III GOJ adenocarcinoma were identified from a Swedish prospective population-based nationwide cohort. The surgical approaches were compared in relation to non-radical resection margins (main outcome) using multivariable logistic regression, providing odds ratios (ORs) and 95% confidence intervals (CIs), mean number of removed lymph nodes with standard deviation (SD) using ANCOVA, assessing mean differences and 95% CIs, and 5-year mortality using Cox regression estimating hazard ratios (HRs) and 95% CIs. The models were adjusted for age, sex, comorbidity, tumour stage, and surgeon volume. The non-radical resection rate was 15% for gastrectomy and 14% for oesophagectomy, and the adjusted OR was 1.61 (95% CI 0.68–3.83). The mean number of lymph nodes removed was 14.2 (SD ± 9.6) for gastrectomy and 14.2 (SD ± 10.4) for oesophagectomy, with adjusted mean difference of 2.4 (95% CI-0.2–5.0). The 5-year mortality was 76% following gastrectomy and 75% following oesophagectomy, with adjusted HR = 1.07 (95% CI 0.78–1.47). Gastrectomy and oesophagectomy for Siewert II or III GOJ cancer seem comparable regarding tumour-free resection margins, lymph nodes removal, and 5-year survival.
ATP-degrading ENPP1 is required for survival (or persistence) of long-lived plasma cells
Authors: Wang Hongsheng , Gonzalez-Garcia Ines , Traba Javier , Jain Shweta , Conteh Solomon , Shin Dong-Mi , Qi Chenfeng , Gao Yuanyuan , Sun Jiafang , Kang Sungyun , Abbasi Sadia , Naghashfar Zohreh , Yoon Jeongheon , DuBois Wendy , Kovalchuk Alexander L. , Sack Michael N. , Duffy Patrick , Morse Herbert C. 
Published: December 2017

AbstractSurvival of antibody-secreting plasma cells (PCs) is vital for sustained antibody production. However, it remains poorly understood how long-lived PCs (LLPCs) are generated and maintained. Here we report that ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) is preferentially upregulated in bone marrow LLPCs compared with their splenic short-lived counterparts (SLPCs). We studied ENPP1-deficient mice (Enpp1−/−) to determine how the enzyme affects PC biology. AlthoughEnpp1−/−mice generated normal levels of germinal center B cells and plasmablasts in periphery, they produced significantly reduced numbers of LLPCs following immunization with T-dependent antigens or infection with plasmodiumC.chabaudi. Bone marrow chimeric mice showed B cell intrinsic effect of ENPP1 selectively on generation of bone marrow as well as splenic LLPCs. Moreover,Enpp1−/−PCs took up less glucose and had lower levels of glycolysis than those of wild-type controls. Thus, ENPP1 deficiency confers an energetic disadvantage to PCs for long-term survival and antibody production.
The pesticide flupyradifurone impairs olfactory learning in Asian honey bees (Apis cerana) exposed as larvae or as adults
Authors: Tan Ken , Wang Cao , Dong Shihao , Li Xinyu , Nieh James C. 
Published: December 2017

AbstractRelatively little attention has focused on how pesticides may affect Asian honey bees, which provide vital crop pollination services and are key native pollinators. We therefore studied the effects of a relatively new pesticide, flupyradifurone (FLU), which has been developed, in part, because it appears safer for honey bees than neonicotinoids. We tested the effects of FLU onApis ceranaolfactory learning in larvae (lower dose of 0.033 µg/larvae/day over 6 days) and, in a separate experiment, adults (lower dose of 0.066 µg/adult bee/day) at sublethal, field-realistic doses given over 3 days. A worst-case field-realistic dose is 0.44 µg/bee/day. Learning was tested in adult bees. The lower larval dose did not increase mortality, but the lower adult dose resulted in 20% mortality. The lower FLU doses decreased average olfactory learning by 74% (larval treatment) and 48% (adult treatment) and reduced average memory by 48% (larval treatment) and 22% (adult treatment) as compared to controls. FLU at higher doses resulted in similar learning impairments. The effects of FLU, a pesticide that is reported to be safer than neonicotinoids for honey bees, thus deserve greater attention.
Image-Guided Fluorescence Endomicroscopy: From Macro- to Micro-Imaging of Radiation-Induced Pulmonary Fibrosis
Authors: Perez Jessica R. , Ybarra Norma , Chagnon Frederic , Serban Monica , Pare Gabriel , Lesur Olivier , Seuntjens Jan , Naqa Issam El 
Published: December 2017

AbstractRadiation-induced pulmonary fibrosis (RIPF) is a debilitating side effect of radiation therapy (RT) of several cancers including lung and breast cancers. Current clinical methods to assess and monitor RIPF involve diagnostic computed tomography (CT) imaging, which is restricted to anatomical macroscopic changes. Confocal laser endomicroscopy (CLE) or fluorescence endomicroscopy (FE) in combination with a fibrosis-targeted fluorescent probe allows to visualize RIPF in real-time at the microscopic level. However, a major limitation of FE imaging is the lack of anatomical localization of the endomicroscope within the lung. In this work, we proposed and validated the use of x-ray fluoroscopy-guidance in a rat model of RIPF to pinpoint the location of the endomicroscope during FE imaging and map it back to its anatomical location in the corresponding CT image. For varying endomicroscope positions, we observed a positive correlation between CT and FE imaging as indicated by the significant association between increased lung density on CT and the presence of fluorescent fiber structures with FE in RT cases compared to Control. Combining multimodality imaging allows visualization and quantification of molecular processes at specific locations within the injured lung. The proposed image-guided FE method can be extended to other disease models and is amenable to clinical translation for assessing and monitoring fibrotic damage.
Inhibition of C1-Ten PTPase activity reduces insulin resistance through IRS-1 and AMPK pathways
Authors: Jeong Heeyoon , Koh Ara , Lee Jiyoun , Park Dohyun , Lee Jung Ok , Lee Mi Nam , Jo Kyung-Jin , Tran Huynh Nguyen Khanh , Kim Eui , Min Byung-Sun , Kim Hyeon Soo , Berggren Per-Olof , Ryu Sung Ho 
Published: December 2017

AbstractInsulin resistance causes type 2 diabetes; therefore, increasing insulin sensitivity is a therapeutic approach against type 2 diabetes. Activating AMP-activated protein kinase (AMPK) is an effective approach for treating diabetes, and reduced insulin receptor substrate-1 (IRS-1) protein levels have been suggested as a molecular mechanism causing insulin resistance. Thus, dual targeting of AMPK and IRS-1 might provide an ideal way to treat diabetes. We found that 15,16-dihydrotanshinone I (DHTS), as a C1-Ten protein tyrosine phosphatase inhibitor, increased IRS-1 stability, improved glucose tolerance and reduced muscle atrophy. Identification of DHTS as a C1-Ten inhibitor revealed a new function of C1-Ten in AMPK inhibition, possibly through regulation of IRS-1. These findings suggest that C1-Ten inhibition by DHTS could provide a novel therapeutic strategy for insulin resistance-associated metabolic syndrome through dual targeting of IRS-1 and AMPK.