bluuebunny/crossref_metadata_2025_split huggingface dataset:
LGR5 regulates gastric adenocarcinoma cell proliferation and invasion via activating Wnt signaling pathway
Authors: Wang Xiangfei , Wang Xiumin , Liu Yang , Dong Yating , Wang Yanan , Kassab Muzaffer Ahmad , Fan Wufang , Yu Xiaochun , Wu Chen 
Published: August 2018

AbstractLGR5 plays a critical role in tissue development and the maintenance of adult stem cells in gastrointestinal tract. However, the oncogenic role of LGR5 in the development of gastric adenocarcinoma remains elusive. Here, we show that LGR5 promotes gastric adenocarcinoma cell proliferation and metastasis. We find that knock down of LGR5 or suppression of Wnt signaling pathway by inhibitor C59 arrests gastric adenocarcinoma cell proliferation and invasion. Moreover, treatment of Wnt3a, the activator of Wnt signaling pathway, partially recovers the proliferation defect observed in LGR5 knockdown gastric adenocarcinoma cells. Moreover, LGR5 facilitates β-catenin nuclear accumulation, a surrogate marker of the activation of Wnt signaling pathway. In addition, C59 treatment suppresses transcription of Axin2 and TCF1, both of which are the target genes of β-catenin in gastric adenocarcinoma cells. Gastric adenocarcinoma cells with overexpressed LGR5 form a large quantity of visible actin filaments and pseudopods, suggesting that LGR5 significantly enhances the ability of cell movement, which might capacitate gastric adenocarcinoma cells with enhanced LGR5 expression to gain invasive and migratory properties. Taken together, our results show that LGR5 contributes to cell proliferation and invasion through the activation of Wnt/β-catenin-signaling pathway in gastric adenocarcinoma cells.
The detrimental effects of glucocorticoids exposure during pregnancy on offspring’s cardiac functions mediated by hypermethylation of bone morphogenetic protein-4
Authors: Peng Jieying , Zhou Yuhao , Zhang Zhiyu , Wang Zhiming , Gao Lingtong , Zhang Xiao , Fang Zhou , Li Guangyao , Chen Huaiyan , Yang Hongxing , Gao Lu 
Published: August 2018

AbstractThe intra-uterine and external environmental factors not only affect the early development of fetuses, their interaction with genesis will also substantially program the physiological functions of offspring throughout life. Synthetic glucocorticoid (GC) is widely used for the management of women at risk of preterm birth or undergone autoimmune diseases. However, excess GC might cause a number of chronic diseases in later life. In the present study, we set up a programming rat model by daily injection of dexamethasone (DEX) since 14.5 dpc until labor, and found that the cardiac functions were significantly compromised in the male offspring compared with that exposed to NS, especially after ischemia/reperfusion (I/R), due to the increased infarction and apoptosis of myocardium. Using MeDIP sequencing, we identified four genes involved in the cardiac muscle cell differentiation and development pathway exhibited increased methylation in their promoter regions, among which, bone morphogenetic protein-4 (BMP4) expression is coordinately decreased in myocardium from male mice prenatally exposed to DEX. The programming effect of DEX on cardiomyocytes apoptosis was found to be dependent on mitochondria dysfunction, whereas the breakdown of mitochondrial membrane potential (ΔΨm) and the decrease of ATP production from mitochondria caused by prenatal DEX exposure both can be restored by BMP4 predisposing on neonatal cardiomyocytes 24 h prior to I/R. Inversely consistent with ΔΨm and ATP production, the release of reactive oxygen species was dramatically elevated in cardiomyocytes, which was significantly inhibited in the presence of BMP4 prior to I/R. These findings suggested that the excess GC exposure during pregnancy increases the susceptibility of male offspring’s heart to “second strike”, due to the decrease of BMP4 expression caused by the hypermethylation on Bmp4 promoter and the absence of BMP4 protective effect in cardiomyocytes, making the addition of BMP4 a promising treatment for the congenital heart disease under such circumstances.
Increased Krüppel-like factor 12 impairs embryo attachment via downregulation of leukemia inhibitory factor in women with recurrent implantation failure
Authors: Huang Chenyang , Sun Haixiang , Wang Zhilong , Liu Yang , Cheng Xi , Liu Jingyu , Jiang Ruiwei , Zhang Xindong , Zhen Xin , Zhou Jidong , Chen Linjun , Ding Lijun , Yan Guijun , Jiang Yue 
Published: August 2018

AbstractRecurrent implantation failure (RIF) caused by various etiological factors remains a challenge for fertility clinicians using assisted reproductive technology (ART) worldwide. Dysregulation of leukemia inhibitory factor (LIF) in the endometria of women with RIF is involved in impaired endometrial receptivity and embryo adhesion. However, the mechanism through which LIF expression is regulated in women with RIF is still poorly understood. Our previous study noted that the abnormally increased endometrial Krüppel-like factor 12 (KLF12) in RIF women led to impaired decidualization and embryo implantation. Here, we further found that KLF12 inhibited embryo adhesion in vivo and in vitro by repressing LIF expression. Mechanistically, KLF12 bound to conserved sites (CAGTGGG, −6771 to −6765 and −7115 to −7109) within the LIF promoter region and repressed LIF transcription directly. Exogenous LIF significantly reversed the KLF12-mediated repression of BeWo spheroid adhesion. KLF12 expression was reduced significantly in Ishikawa cells treated with progestogen, which was due to the activation of Akt signaling. These findings may provide novel potential therapeutic regimens for patients with RIF and disrupted endometrial receptivity.
A dormant TIL phenotype defines non-small cell lung carcinomas sensitive to immune checkpoint blockers
Authors: Gettinger S. N. , Choi J. , Mani N. , Sanmamed M. F. , Datar I. , Sowell Ryan , Du Victor Y. , Kaftan E. , Goldberg S. , Dong W. , Zelterman D. , Politi K. , Kavathas P. , Kaech S. , Yu X. , Zhao H. , Schlessinger J. , Lifton R. , Rimm D. L. , Chen L. , Herbst R. S. , Schalper K. A. 
Published: August 2018

AbstractThe biological determinants of sensitivity and resistance to immune checkpoint blockers are not completely understood. To elucidate the role of intratumoral T-cells and their association with the tumor genomic landscape, we perform paired whole exome DNA sequencing and multiplexed quantitative immunofluorescence (QIF) in pre-treatment samples from non-small cell lung carcinoma (NSCLC) patients treated with PD-1 axis blockers. QIF is used to simultaneously measure the level of CD3+ tumor infiltrating lymphocytes (TILs), in situ T-cell proliferation (Ki-67 in CD3) and effector capacity (Granzyme-B in CD3). Elevated mutational load, candidate class-I neoantigens or intratumoral CD3 signal are significantly associated with favorable response to therapy. Additionally, a “dormant” TIL signature is associated with survival benefit in patients treated with immune checkpoint blockers characterized by elevated TILs with low activation and proliferation. We further demonstrate that dormant TILs can be reinvigorated upon PD-1 blockade in a patient-derived xenograft model.
Multiple timescales of normalized value coding underlie adaptive choice behavior
Authors: Zimmermann Jan , Glimcher Paul W. , Louie Kenway 
Published: August 2018

AbstractAdaptation is a fundamental process crucial for the efficient coding of sensory information. Recent evidence suggests that similar coding principles operate in decision-related brain areas, where neural value coding adapts to recent reward history. However, the circuit mechanism for value adaptation is unknown, and the link between changes in adaptive value coding and choice behavior is unclear. Here we show that choice behavior in nonhuman primates varies with the statistics of recent rewards. Consistent with efficient coding theory, decision-making shows increased choice sensitivity in lower variance reward environments. Both the average adaptation effect and across-session variability are explained by a novel multiple timescale dynamical model of value representation implementing divisive normalization. The model predicts empirical variance-driven changes in behavior despite having no explicit knowledge of environmental statistics, suggesting that distributional characteristics can be captured by dynamic model architectures. These findings highlight the importance of treating decision-making as a dynamic process and the role of normalization as a unifying computation for contextual phenomena in choice.
Understanding the apparent fractional charge of protons in the aqueous electrochemical double layer
Authors: Chen Leanne D. , Bajdich Michal , Martirez J. Mark P. , Krauter Caroline M. , Gauthier Joseph A. , Carter Emily A. , Luntz Alan C. , Chan Karen , Nørskov Jens K. 
Published: August 2018

AbstractA detailed atomic-scale description of the electrochemical interface is essential to the understanding of electrochemical energy transformations. In this work, we investigate the charge of solvated protons at the Pt(111) | H2O and Al(111) | H2O interfaces. Using semi-local density-functional theory as well as hybrid functionals and embedded correlated wavefunction methods as higher-level benchmarks, we show that the effective charge of a solvated proton in the electrochemical double layer or outer Helmholtz plane at all levels of theory is fractional, when the solvated proton and solvent band edges are aligned correctly with the Fermi level of the metal (EF). The observed fractional charge in the absence of frontier band misalignment arises from a significant overlap between the proton and the electron density from the metal surface, and results in an energetic difference between protons in bulk solution and those in the outer Helmholtz plane.
N2 activation on a molybdenum–titanium–sulfur cluster
Authors: Ohki Yasuhiro , Uchida Keisuke , Tada Mizuki , Cramer Roger E. , Ogura Takashi , Ohta Takehiro 
Published: August 2018

AbstractThe FeMo-cofactor of nitrogenase, a metal–sulfur cluster that contains eight transition metals, promotes the conversion of dinitrogen into ammonia when stored in the protein. Although various metal–sulfur clusters have been synthesized over the past decades, their use in the activation of N2 has remained challenging, and even the FeMo-cofactor extracted from nitrogenase is not able to reduce N2. Herein, we report the activation of N2 by a metal–sulfur cluster that contains molybdenum and titanium. An N2 moiety bridging two [Mo3S4Ti] cubes is converted into NH3 and N2H4 upon treatment with Brønsted acids in the presence of a reducing agent.
Long-term deep-supercooling of large-volume water and red cell suspensions via surface sealing with immiscible liquids
Authors: Huang Haishui , Yarmush Martin L. , Usta O. Berk 
Published: August 2018

AbstractSupercooling of aqueous solutions is a fundamentally and practically important physical phenomenon with numerous applications in biopreservation and beyond. Under normal conditions, heterogeneous nucleation mechanisms critically prohibit the simultaneous long-term (> 1 week), large volume (> 1 ml), and low temperatures (< −10 °C) supercooling of aqueous solutions. Here, we report on the use of surface sealing of water by an oil phase to significantly diminish the primary heterogeneous nucleation at the water/air interface. We achieve deep supercooling (down to −20 °C) of large volumes of water (up to 100 ml) for long periods (up to 100 days) simultaneously via this approach. Since oils are mixtures of various hydrocarbons we also report on the use of pure alkanes and primary alcohols of various lengths to achieve the same. Furthermore, we demonstrate the utility of deep supercooling via preliminary studies on extended (100 days) preservation of human red blood cells.
Maximal viral information recovery from sequence data using VirMAP
Authors: Ajami Nadim J , Wong Matthew C. , Ross Matthew C. , Lloyd Richard E. , Petrosino Joseph F. 
Published: August 2018

AbstractAccurate classification of the human virome is critical to a full understanding of the role viruses play in health and disease. This implies the need for sensitive, specific, and practical pipelines that return precise outputs while still enabling case-specific post hoc analysis. Viral taxonomic characterization from metagenomic data suffers from high background noise and signal crosstalk that confounds current methods. Here we develop VirMAP that overcomes these limitations using techniques that merge nucleotide and protein information to taxonomically classify viral reconstructions independent of genome coverage or read overlap. We validate VirMAP using published data sets and viral mock communities containing RNA and DNA viruses and bacteriophages. VirMAP offers opportunities to enhance metagenomic studies seeking to define virome-host interactions, improve biosurveillance capabilities, and strengthen molecular epidemiology reporting.
Lensfree OLEDs with over 50% external quantum efficiency via external scattering and horizontally oriented emitters
Authors: Song Jinouk , Kim Kwon-Hyeon , Kim Eunhye , Moon Chang-Ki , Kim Yun-Hi , Kim Jang-Joo , Yoo Seunghyup 
Published: August 2018

AbstractHigh efficiency is important for successful deployment of any light sources. Continued efforts have recently made it possible to demonstrate organic light-emitting diodes with efficiency comparable to that of inorganic light-emitting diodes. However, such achievements were possible only with the help of a macroscopic lens or complex internal nanostructures, both of which undermine the key benefits of organic light-emitting diodes as an affordable planar light source. Here we present a systematic way to achieve organic light-emitting diodes with ultrahigh efficiency even only with an external scattering film, one of the simplest low-cost outcoupling structures. Through a global, multivariable analysis, we show that scattering with a high degree of forwardness has a potential to play a critical role in realizing ultimate efficiency. Combined with horizontally oriented emitters, organic light-emitting diodes equipped with particle-embedded films tailored for forward-intensive scattering achieve a maximum external quantum efficiency of 56%.
Capacitive neural network with neuro-transistors
Authors: Wang Zhongrui , Rao Mingyi , Han Jin-Woo , Zhang Jiaming , Lin Peng , Li Yunning , Li Can , Song Wenhao , Asapu Shiva , Midya Rivu , Zhuo Ye , Jiang Hao , Yoon Jung Ho , Upadhyay Navnidhi Kumar , Joshi Saumil , Hu Miao , Strachan John Paul , Barnell Mark , Wu Qing , Wu Huaqiang , Qiu Qinru , Williams R. Stanley , Xia Qiangfei , Yang J. Joshua 
Published: August 2018

AbstractExperimental demonstration of resistive neural networks has been the recent focus of hardware implementation of neuromorphic computing. Capacitive neural networks, which call for novel building blocks, provide an alternative physical embodiment of neural networks featuring a lower static power and a better emulation of neural functionalities. Here, we develop neuro-transistors by integrating dynamic pseudo-memcapacitors as the gates of transistors to produce electronic analogs of the soma and axon of a neuron, with “leaky integrate-and-fire” dynamics augmented by a signal gain on the output. Paired with non-volatile pseudo-memcapacitive synapses, a Hebbian-like learning mechanism is implemented in a capacitive switching network, leading to the observed associative learning. A prototypical fully integrated capacitive neural network is built and used to classify inputs of signals.
Biology and genome of a newly discovered sibling species of Caenorhabditis elegans
Authors: Kanzaki Natsumi , Tsai Isheng J. , Tanaka Ryusei , Hunt Vicky L. , Liu Dang , Tsuyama Kenji , Maeda Yasunobu , Namai Satoshi , Kumagai Ryohei , Tracey Alan , Holroyd Nancy , Doyle Stephen R. , Woodruff Gavin C. , Murase Kazunori , Kitazume Hiromi , Chai Cynthia , Akagi Allison , Panda Oishika , Ke Huei-Mien , Schroeder Frank C. , Wang John , Berriman Matthew , Sternberg Paul W. , Sugimoto Asako , Kikuchi Taisei 
Published: August 2018

AbstractA ‘sibling’ species of the model organism Caenorhabditis elegans has long been sought for use in comparative analyses that would enable deep evolutionary interpretations of biological phenomena. Here, we describe the first sibling species of C. elegans, C. inopinata n. sp., isolated from fig syconia in Okinawa, Japan. We investigate the morphology, developmental processes and behaviour of C. inopinata, which differ significantly from those of C. elegans. The 123-Mb C. inopinata genome was sequenced and assembled into six nuclear chromosomes, allowing delineation of Caenorhabditis genome evolution and revealing unique characteristics, such as highly expanded transposable elements that might have contributed to the genome evolution of C. inopinata. In addition, C. inopinata exhibits massive gene losses in chemoreceptor gene families, which could be correlated with its limited habitat area. We have developed genetic and molecular techniques for C. inopinata; thus C. inopinata provides an exciting new platform for comparative evolutionary studies.
Atomic engineering of high-density isolated Co atoms on graphene with proximal-atom controlled reaction selectivity
Authors: Yan Huan , Zhao Xiaoxu , Guo Na , Lyu Zhiyang , Du Yonghua , Xi Shibo , Guo Rui , Chen Cheng , Chen Zhongxin , Liu Wei , Yao Chuanhao , Li Jing , Pennycook Stephen J. , Chen Wei , Su Chenliang , Zhang Chun , Lu Jiong 
Published: August 2018

AbstractControllable synthesis of single atom catalysts (SACs) with high loading remains challenging due to the aggregation tendency of metal atoms as the surface coverage increases. Here we report the synthesis of graphene supported cobalt SACs (Co1/G) with a tuneable high loading by atomic layer deposition. Ozone treatment of the graphene support not only eliminates the undesirable ligands of the pre-deposited metal precursors, but also regenerates active sites for the precise tuning of the density of Co atoms. The Co1/G SACs also demonstrate exceptional activity and high selectivity for the hydrogenation of nitroarenes to produce azoxy aromatic compounds, attributable to the formation of a coordinatively unsaturated and positively charged catalytically active center (Co–O–C) arising from the proximal-atom induced partial depletion of the 3d Co orbitals. Our findings pave the way for the precise engineering of the metal loading in a variety of SACs for superior catalytic activities.
Surgical Standards for Management of the Axilla in Breast Cancer Clinical Trials with Pathological Complete Response Endpoint
Authors: Boughey Judy C. , Alvarado Michael D. , Lancaster Rachael B. , Fraser Symmans W. , Mukhtar Rita , Wong Jasmine M. , Ewing Cheryl A. , Potter David A. , Tuttle Todd M. , Hieken Tina J. , Carter Jodi M. , Jakub James W. , Kaplan Henry G. , Buchanan Claire L. , Jaskowiak Nora T. , Sattar Husain A. , Mueller Jeffrey , Nanda Rita , Isaacs Claudine J. , Pohlmann Paula R. , Lynce Filipa , Tousimis Eleni A. , Zeck Jay C. , Lee M. Catherine , Lang Julie E. , Mhawech-Fauceglia Paulette , Rao Roshni , Taback Bret , Godellas Constantine , Chen Margaret , Kalinsky Kevin M. , Hibshoosh Hanina , Killelea Brigid , Sanft Tara , Hirst Gillian L. , Asare Smita , Matthews Jeffrey B. , Perlmutter Jane , Esserman Laura J. ,   and I-SPY 2 Investigators, Chien A. Jo , Forero-Torres Andres , Yee Douglas , Ellis Erin D. , Han Heather S. , Lu Janice , Wallace Anne M. , Albain Kathy S. , Elias Anthony D. , Clark Amy S. , Kemmer Kathleen 
Published: August 2018

AbstractAdvances in the surgical management of the axilla in patients treated with neoadjuvant chemotherapy, especially those with node positive disease at diagnosis, have led to changes in practice and more judicious use of axillary lymph node dissection that may minimize morbidity from surgery. However, there is still significant confusion about how to optimally manage the axilla, resulting in variation among practices. From the viewpoint of drug development, assessment of response to neoadjuvant chemotherapy remains paramount and appropriate assessment of residual disease—the primary endpoint of many drug therapy trials in the neoadjuvant setting—is critical. Therefore decreasing the variability, especially in a multicenter clinical trial setting, and establishing a minimum standard to ensure consistency in clinical trial data, without mandating axillary lymph node dissection, for all patients is necessary. The key elements which include proper staging and identification of nodal involvement at diagnosis, and appropriately targeted management of the axilla at the time of surgical resection are presented. The following protocols have been adopted as standard procedure by the I-SPY2 trial for management of axilla in patients with node positive disease, and present a framework for prospective clinical trials and practice.
Microgelation imparts emulsifying ability to surface-inactive polysaccharides—bottom-up vs top-down approaches
Authors: Ishii Toya , Matsumiya Kentaro , Aoshima Mai , Matsumura Yasuki 
Published: August 2018

AbstractIn order to impart emulsifying ability to gel-forming polysaccharides that have not been used as emulsifying agents, three kinds of polysaccharides, agar, curdlan, and gellan gum were converted to microgels by different gelation methods via the bottom-up and top-down approaches. We clearly demonstrated that agar and curdlan acquired the ability to emulsify an edible oil by microgel formation. Among the colloidal properties of microgel suspensions such as microstructure, particle size, zeta-potential, viscosity, and surface hydrophobicity, we pointed out the importance of particle size on the emulsifying ability of polysaccharide-based microgels. The creaming behavior of the microgel-stabilized emulsions depended on the polysaccharide types and microgel preparation methods. The emulsion stability against oil droplet coalescence was extremely high for agar and curdlan microgel-stabilized emulsions during storage in the static condition, whereas different stability was observed for both the emulsions, that is, the curdlan microgel-based ones were more resistant to dynamic forcible destabilization by centrifugation than the agar ones, which can be attributed to the surface hydrophobicity of the microgels.
AEBP1 promotes epithelial-mesenchymal transition of gastric cancer cells by activating the NF-κB pathway and predicts poor outcome of the patients
Authors: Liu Jun-yan , Jiang Lei , Liu Jia-jia , He Tao , Cui You-hong , Qian Feng , Yu Pei-wu 
Published: August 2018

AbstractAdipocyte enhancer binding protein 1 (AEBP1) is a transcriptional repressor that plays a critical role in regulating adipogenesis. Recent studies have indicated that AEBP1 might function as a candidate oncogene and is overexpressed in several human malignancies. However, the role of AEBP1 in gastric cancer (GC) remains largely unknown. This study aimed to investigate the expression pattern, prognostic significance and biological function of AEBP1 in human gastric cancer and to explore the underlying mechanism. We found that both the mRNA and protein levels of AEBP1 were significantly increased in human GC tissues. Elevated AEBP1 expression was significantly correlated with poor overall survival in patients with both early-stage (Tumor, Node, Metastases (TNM) TNM I and II) and late-stage (TNM III and IV) GC. Silencing AEBP1 markedly suppressed the proliferation, migration, invasion, metastasis and epithelial-mesenchymal transition of GC cells. Moreover, we demonstrated that knockdown of AEBP1 in GC cells led to inhibition of the NF-κB pathway by hampering the degradation of IκBα. Thus, AEBP1 might be served as a promising prognostic indicator and a potential therapeutic target in human GC.