bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long noncoding RNA MEG3 suppresses liver cancer cells growth through inhibiting β-catenin by activating PKM2 and inactivating PTEN
Authors: Zheng Qidi , Lin Zhuojia , Xu Jie , Lu Yanan , Meng Qiuyu , Wang Chen , Yang Yuxin , Xin Xiaoru , Li Xiaonan , Pu Hu , Gui Xin , Li Tianming , Xiong Wujun , Lu Dongdong 
Published: February 2018

AbstractMaternally expressed gene 3 (MEG3) encodes an lncRNA which is suggested to function as a tumor suppressor and has been showed to involve in a variety of cancers. Herein, our findings demonstrate that MEG3 inhibits the malignant progression of liver cancer cells in vitro and in vivo. Mechanistically, MEG3 promotes the expression and maturition of miR122 which targets PKM2. Therefore, MEG3 decreases the expression and nuclear location of PKM2 dependent on miR122. Furthermore, MEG3 also inhibits CyclinD1 and C-Myc via PKM2 in liver cancer cells. On the other hand, MEG3 promotes β-catenin degradation through ubiquitin–proteasome system dependent on PTEN. Strikingly, MEG3 inhibits β-catenin activity through PKM2 reduction and PTEN increase. Significantly, we also found that excessive β-catenin abrogated the effect of MEG3 in liver cancer. In conclusion, our study for the first time demonstrates that MEG3 acts as a tumor suppressor by negatively regulating the activity of the PKM2 and β-catenin signaling pathway in hepatocarcinogenesis and could provide potential therapeutic targets for the treatment of liver cancer.
Rhinovirus 3C protease suppresses apoptosis and triggers caspase-independent cell death
Authors: Lötzerich Mark , Roulin Pascal S. , Boucke Karin , Witte Robert , Georgiev Oleg , Greber Urs F. 
Published: February 2018

AbstractApoptosis and programmed necrosis (necroptosis) determine cell fate, and antagonize infection. Execution of these complementary death pathways involves the formation of receptor-interacting protein kinase 1 (RIPK1) containing complexes. RIPK1 binds to adaptor proteins, such as TRIF (Toll-IL-1 receptor-domain-containing-adaptor-inducing interferon-beta factor), FADD (Fas-associated-protein with death domain), NEMO (NF-κB regulatory subunit IKKγ), SQSTM1 (sequestosome 1/p62), or RIPK3 (receptor-interacting protein kinase 3), which are involved in RNA sensing, NF-κB signaling, autophagosome formation, apoptosis, and necroptosis. We report that a range of rhinoviruses impair apoptosis and necroptosis in epithelial cells late in infection. Unlike the double-strand (ds) RNA mimetic poly I:C (polyinosinic:polycytidylic acid), the exposure of dsRNA to toll-like receptor 3 (TLR3) in rhinovirus-infected cells did not lead to apoptosis execution. Accordingly, necroptosis and the production of ROS (reactive oxygen species) were not observed late in infection, when RIPK3 was absent. Instead, a virus-induced alternative necrotic cell death pathway proceeded, which led to membrane rupture, indicated by propidium iodide staining. The impairment of dsRNA-induced apoptosis late in infection was controlled by the viral 3C-protease (3Cpro), which disrupted RIPK1-TRIF/FADD /SQSTM1 immune-complexes. 3Cpro and 3C precursors were found to coimmuno-precipitate with RIPK1, cleaving the RIPK1 death-domain, and generating N-terminal RIPK1 fragments. The depletion of RIPK1 or chemical inhibition of its kinase at the N-terminus did not interfere with virus progeny formation or cell fate. The data show that rhinoviruses suppress apoptosis and necroptosis, and release progeny by an alternative cell death pathway, which is controlled by viral proteases modifying innate immune complexes.
Downregulation of SREBP inhibits tumor growth and initiation by altering cellular metabolism in colon cancer
Authors: Wen Yang-An , Xiong Xiaopeng , Zaytseva Yekaterina Y. , Napier Dana L. , Vallee Emma , Li Austin T. , Wang Chi , Weiss Heidi L. , Evers B. Mark , Gao Tianyan 
Published: February 2018

AbstractSterol regulatory element-binding proteins (SREBPs) belong to a family of transcription factors that regulate the expression of genes required for the synthesis of fatty acids and cholesterol. Three SREBP isoforms, SREBP1a, SREBP1c, and SREBP2, have been identified in mammalian cells. SREBP1a and SREBP1c are derived from a single gene through the use of alternative transcription start sites. Here we investigated the role of SREBP-mediated lipogenesis in regulating tumor growth and initiation in colon cancer. Knockdown of either SREBP1 or SREBP2 decreased levels of fatty acids as a result of decreased expression of SREBP target genes required for lipid biosynthesis in colon cancer cells. Bioenergetic analysis revealed that silencing SREBP1 or SREBP2 expression reduced the mitochondrial respiration, glycolysis, as well as fatty acid oxidation indicating an alteration in cellular metabolism. Consequently, the rate of cell proliferation and the ability of cancer cells to form tumor spheroids in suspension culture were significantly decreased. Similar results were obtained in colon cancer cells in which the proteolytic activation of SREBP was blocked. Importantly, knockdown of either SREBP1 or SREBP2 inhibited xenograft tumor growth in vivo and decreased the expression of genes associated with cancer stem cells. Taken together, our findings establish the molecular basis of SREBP-dependent metabolic regulation and provide a rationale for targeting lipid biosynthesis as a promising approach in colon cancer treatment.
Knockout of zebrafish interleukin 7 receptor (IL7R) by the CRISPR/Cas9 system delays retinal neurodevelopment
Authors: Cai Shijiao , Chen Yang , Shang Yue , Cui Jianlin , Li Zongjin , Li Yuhao 
Published: February 2018

AbstractInterleukin 7 receptor (il7r), a transmembrane receptor, belongs to the type I cytokine receptor family. Il7r is involved in the pathogenesis of neurodegenerative disorders, such as multiple sclerosis. Targeted knockdown of il7r leads to delayed myelination, highlighting the potential role of il7r in the development of the nervous system. Zebrafish is an ideal model for the study of neurogenesis; moreover, the il7r gene is highly conserved between zebrafish and human. The aim of the present study was to investigate the novel function of il7r in neurogenesis. First, an il7r−/− homozygous mutant line was generated by clustered regularly interspaced short palindromic repeats (CRISPR)-associated 9 (CRISPR/Cas9) technology. Second, the gross development of il7r−/− mutants revealed remarkably smaller eyes and delayed retinal neurodifferentiation. Third, microarray analysis revealed that genes associated with the phototransduction signalling pathway were strongly down-regulated in il7r−/− mutants. Finally, the results from behavioural tests indicated that visual function was impaired in il7r−/− mutant larvae. Overall, our data demonstrate that a lack of il7r retards the development of the retina. Thus, il7r is an essential molecule for maintaining normal retinal development in zebrafish.
High-performance graphdiyne-based electrochemical actuators
Authors: Lu Chao , Yang Ying , Wang Jian , Fu Ruoping , Zhao Xinxin , Zhao Lei , Ming Yue , Hu Ying , Lin Hongzhen , Tao Xiaoming , Li Yuliang , Chen Wei 
Published: February 2018

AbstractElectrochemical actuators directly converting electrical energy to mechanical energy are critically important for artificial intelligence. However, their energy transduction efficiency is always lower than 1.0% because electrode materials lack active units in microstructure, and their assembly systems can hardly express the intrinsic properties. Here, we report a molecular-scale active graphdiyne-based electrochemical actuator with a high electro-mechanical transduction efficiency of up to 6.03%, exceeding that of the best-known piezoelectric ceramic, shape memory alloy and electroactive polymer reported before, and its energy density (11.5 kJ m−3) is comparable to that of mammalian skeletal muscle (~8 kJ m−3). Meanwhile, the actuator remains responsive at frequencies from 0.1 to 30 Hz with excellent cycling stability over 100,000 cycles. Furthermore, we verify the alkene–alkyne complex transition effect responsible for the high performance through in situ sum frequency generation spectroscopy. This discovery sheds light on our understanding of actuation mechanisms and will accelerate development of smart actuators.
Dynamic air/liquid pockets for guiding microscale flow
Authors: Hou Xu , Li Jianyu , Tesler Alexander B. , Yao Yuxing , Wang Miao , Min Lingli , Sheng Zhizhi , Aizenberg Joanna 
Published: February 2018

AbstractMicroscale flows of fluids are mainly guided either by solid matrices or by liquid–liquid interfaces. However, the solid matrices are plagued with persistent fouling problems, while liquid–liquid interfaces are limited to low-pressure applications. Here we report a dynamic liquid/solid/gas material containing both air and liquid pockets, which are formed by partially infiltrating a porous matrix with a functional liquid. Using detailed theoretical and experimental data, we show that the distribution of the air- and liquid-filled pores is responsive to pressure and enables the formation and instantaneous recovery of stable liquid–liquid interfaces that sustain a wide range of pressures and prevent channel contamination. This adaptive design is demonstrated for polymeric materials and extended to metal-based systems that can achieve unmatched mechanical and thermal stability. Our platform with its unique adaptive pressure and antifouling capabilities may offer potential solutions to flow control in microfluidics, medical devices, microscale synthesis, and biological assays.
Clove Bud Oil Modulates Pathogenicity Phenotypes of the Opportunistic Human Pathogen Pseudomonas aeruginosa
Authors: Haripriyan Jayalekshmi , Omanakuttan Athira , Menon Nitasha D. , Vanuopadath Muralidharan , Nair Sudarslal Sadasivan , Corriden Ross , Nair Bipin G. , Nizet Victor , Kumar Geetha B. 
Published: February 2018

AbstractEarlier studies from our laboratory have demonstrated that clove bud oil (CBO) attenuates expression of certain virulence factors of Pseudomonas aeruginosa PAO1. Here, we probe more deeply into the effect of CBO on four pseudomonal proteases - elastase A, elastase B, protease IV and alkaline protease - each known to play key roles in disease pathogenesis. CBO inhibited the activity of these proteases present in the bacterial culture supernatant. Zymography studies indicated that these proteases can activate host matrix metalloproteases (MMPs) to establish infection, through conversion of pro-MMP-2 to active MMP-2. PAO1 is a predominant pathogen in burn wound infections and we show the modulatory effect of CBO on MMPs in an in vitro model of burn injury. Furthermore, CBO induced dose-dependent neutrophil extracellular trap formation in human neutrophils. CBO also increased the survival of C. elegans infected with PAO1, establishing an anti-infective role in a whole animal model of pathogenesis. LC-MS/MS analysis indicated that CBO treatment elicited a significant reduction of signalling molecules (Acyl-Homoserine-Lactone) involved in quorum sensing regulation. Our observations demonstrate that CBO attenuates key virulence mechanisms of this important human pathogen, while concomitantly enhancing host innate immunomodulatory functions, with potential implications for topical therapy against antibiotic-resistant infections.
Network analysis of coronary artery disease risk genes elucidates disease mechanisms and druggable targets
Authors: Lempiäinen Harri , Brænne Ingrid , Michoel Tom , Tragante Vinicius , Vilne Baiba , Webb Tom R. , Kyriakou Theodosios , Eichner Johannes , Zeng Lingyao , Willenborg Christina , Franzen Oscar , Ruusalepp Arno , Goel Anuj , van der Laan Sander W. , Biegert Claudia , Hamby Stephen , Talukdar Husain A. , Foroughi Asl Hassan ,   CVgenes@target consortium, Dichgans Martin , Dreker Tobias , Graettinger Mira , Gribbon Philip , Kessler Thorsten , Malik Rainer , Prestel Matthias , Stiller Barbara , Schofield Christine , Pasterkamp Gerard , Watkins Hugh , Samani Nilesh J. , Wittenberger Timo , Erdmann Jeanette , Schunkert Heribert , Asselbergs Folkert W. , Björkegren Johan L. M. 
Published: February 2018

AbstractGenome-wide association studies (GWAS) have identified over two hundred chromosomal loci that modulate risk of coronary artery disease (CAD). The genes affected by variants at these loci are largely unknown and an untapped resource to improve our understanding of CAD pathophysiology and identify potential therapeutic targets. Here, we prioritized 68 genes as the most likely causal genes at genome-wide significant loci identified by GWAS of CAD and examined their regulatory roles in 286 metabolic and vascular tissue gene-protein sub-networks (“modules”). The modules and genes within were scored for CAD druggability potential. The scoring enriched for targets of cardiometabolic drugs currently in clinical use and in-depth analysis of the top-scoring modules validated established and revealed novel target tissues, biological processes, and druggable targets. This study provides an unprecedented resource of tissue-defined gene–protein interactions directly affected by genetic variance in CAD risk loci.
Exogenous nitric oxide stimulates the odontogenic differentiation of rat dental pulp stem cells
Authors: Sonoda Soichiro , Mei Yu-feng , Atsuta Ikiru , Danjo Atsushi , Yamaza Haruyoshi , Hama Shion , Nishida Kento , Tang Ronghao , Kyumoto-Nakamura Yukari , Uehara Norihisa , Kukita Toshio , Nishimura Fusanori , Yamaza Takayoshi 
Published: February 2018

AbstractNitric oxide (NO) is thought to play a pivotal regulatory role in dental pulp tissues under both physiological and pathological conditions. However, little is known about the NO functions in dental pulp stem cells (DPSCs). We examined the direct actions of a spontaneous NO gas-releasing donor, NOC-18, on the odontogenic capacity of rat DPSCs (rDPSCs). In the presence of NOC-18, rDPSCs were transformed into odontoblast-like cells with long cytoplasmic processes and a polarized nucleus. NOC-18 treatment increased alkaline phosphatase activity and enhanced dentin-like mineralized tissue formation and the expression levels of several odontoblast-specific genes, such as runt related factor 2, dentin matrix protein 1 and dentin sialophosphoprotein, in rDPSCs. In contrast, carboxy-PTIO, a NO scavenger, completely suppressed the odontogenic capacity of rDPSCs. This NO-promoted odontogenic differentiation was activated by tumor necrosis factor-NF-κB axis in rDPSCs. Further in vivo study demonstrated that NOC-18-application in a tooth cavity accelerated tertiary dentin formation, which was associated with early nitrotyrosine expression in the dental pulp tissues beneath the cavity. Taken together, the present findings indicate that exogenous NO directly induces the odontogenic capacity of rDPSCs, suggesting that NO donors might offer a novel host DPSC-targeting alternative to current pulp capping agents in endodontics.
Alcohol Impairs N100 Response to Dorsolateral Prefrontal Cortex Stimulation
Authors: Loheswaran Genane , Barr Mera S. , Zomorrodi Reza , Rajji Tarek K. , Blumberger Daniel M. , Le Foll Bernard , Daskalakis Zafiris J. 
Published: February 2018

AbstractAlcohol is thought to exert its effect by acting on gamma-aminobutyric (GABA) inhibitory neurotransmission. The N100, the negative peak on electroencephalography (EEG) that occurs approximately 100 ms following the transcranial magnetic stimulation (TMS) pulse, is believed to represent GABAB receptor mediated neurotransmission. However, no studies have examined the effect of alcohol on the N100 response to TMS stimulation of the dorsolateral prefrontal cortex (DLPFC). In the present study, we aimed to explore the effect of alcohol on the DLPFC TMS-evoked N100 response. The study was a within-subject cross-over design study. Fifteen healthy alcohol drinkers were administered TMS to the DLPFC before (PreBev) and after consumption (PostBev) of an alcohol or placebo beverage. The amplitude of the N100 before and after beverage was compared for both the alcohol and placebo beverage. Alcohol produced a significant decrease in N100 amplitude (t = 4.316, df = 14, p = 0.001). The placebo beverage had no effect on the N100 amplitude (t = −1.856, df = 14, p = 0.085). Acute alcohol consumption produces a decrease in N100 amplitude to TMS stimulation of the DLPFC, suggesting a decrease in GABAB receptor mediated neurotransmission. Findings suggest that the N100 may represent a marker of alcohol’s effects on inhibitory neurotransmission.
Predatory flying squids are detritivores during their early planktonic life
Authors: Fernández-Álvarez Fernando Á. , Machordom Annie , García-Jiménez Ricardo , Salinas-Zavala César A. , Villanueva Roger 
Published: February 2018

AbstractCephalopods are primarily active predators throughout life. Flying squids (family Ommastrephidae) represents the most widely distributed and ecologically important family of cephalopods. While the diets of adult flying squids have been extensively studied, the first feeding diet of early paralarvae remains a mystery. The morphology of this ontogenetic stage notably differs from other cephalopod paralarvae, suggesting a different feeding strategy. Here, a combination of Laser Capture Microdissection (LCM) and DNA metabarcoding of wild-collected paralarvae gut contents for eukaryotic 18S v9 and prokaryotic 16S rRNA was applied, covering almost every life domain. The gut contents were mainly composed by fungus, plants, algae and animals of marine and terrestrial origin, as well as eukaryotic and prokaryotic microorganisms commonly found in fecal pellets and particulate organic matter. This assemblage of gut contents is consistent with a diet based on detritus. The ontogenetic shift of diet from detritivore suspension feeding to active predation represents a unique life strategy among cephalopods and allows ommastrephid squids to take advantage of an almost ubiquitous and accessible food resource during their early stages. LCM was successfully applied for the first time to tiny, wild-collected marine organisms, proving its utility in combination with DNA metabarcoding for dietary studies.
Phosphorus addition changes belowground biomass and C:N:P stoichiometry of two desert steppe plants under simulated N deposition
Authors: Huang Juying , Yu Hailong , Liu Jili , Luo Chengke , Sun Zhaojun , Ma Kaibo , Kang Yangmei , Du Yaxian 
Published: February 2018

AbstractMany studies have reported that increasing atmospheric nitrogen (N) deposition broadens N:phosphorus (P) in both soils and plant leaves and potentially intensifies P limitation for plants. However, few studies have tested whether P addition alleviates N-induced P limitation for plant belowground growth. It is also less known how changed N:P in soils and leaves affect plant belowground stoichiometry, which is significant for maintaining key belowground ecological processes. We conducted a multi-level N:P supply experiment (varied P levels combined with constant N amount) for Glycyrrhiza uralensis (a N fixing species) and Pennisetum centrasiaticum (a grass) from a desert steppe in Northwest China during 2011–2013. Results showed that increasing P addition increased the belowground biomass and P concentrations of both species, resulting in the decreases in belowground carbon (C):P and N:P. These results indicate that P inputs alleviated N-induced P limitation and hence stimulated belowground growth. Belowground C:N:P stoichiometry of both species, especially P. centrasiaticum, tightly linked to soil and green leaf C:N:P stoichiometry. Thus, the decoupling of C:N:P ratios in both soils and leaves under a changing climate could directly alter plant belowground stoichiometry, which will in turn have important feedbacks to primary productivity and C sequestration.
Lifetime of racetrack skyrmions
Authors: Bessarab Pavel F. , Müller Gideon P. , Lobanov Igor S. , Rybakov Filipp N. , Kiselev Nikolai S. , Jónsson Hannes , Uzdin Valery M. , Blügel Stefan , Bergqvist Lars , Delin Anna 
Published: February 2018

AbstractThe skyrmion racetrack is a promising concept for future information technology. There, binary bits are carried by nanoscale spin swirls–skyrmions–driven along magnetic strips. Stability of the skyrmions is a critical issue for realising this technology. Here we demonstrate that the racetrack skyrmion lifetime can be calculated from first principles as a function of temperature, magnetic field and track width. Our method combines harmonic transition state theory extended to include Goldstone modes, with an atomistic spin Hamiltonian parametrized from density functional theory calculations. We demonstrate that two annihilation mechanisms contribute to the skyrmion stability: At low external magnetic field, escape through the track boundary prevails, but a crossover field exists, above which the collapse in the interior becomes dominant. Considering a Pd/Fe bilayer on an Ir(111) substrate as a well-established model system, the calculated skyrmion lifetime is found to be consistent with reported experimental measurements. Our simulations also show that the Arrhenius pre-exponential factor of escape depends only weakly on the external magnetic field, whereas the pre-exponential factor for collapse is strongly field dependent. Our results open the door for predictive simulations, free from empirical parameters, to aid the design of skyrmion-based information technology.
Assessment of novel vaccination regimens using viral vectored liver stage malaria vaccines encoding ME-TRAP
Authors: Bliss Carly M. , Bowyer Georgina , Anagnostou Nicholas A. , Havelock Tom , Snudden Claudia M. , Davies Huw , de Cassan Simone C. , Grobbelaar Amy , Lawrie Alison M. , Venkatraman Navin , Poulton Ian D. , Roberts Rachel , Mange Pooja B. , Choudhary Prateek , Faust Saul N. , Colloca Stefano , Gilbert Sarah C. , Nicosia Alfredo , Hill Adrian V. S. , Ewer Katie J. 
Published: February 2018

AbstractHeterologous prime-boost vaccination with viral vectors simian adenovirus 63 (ChAd63) and Modified Vaccinia Ankara (MVA) induces potent T cell and antibody responses in humans. The 8-week regimen demonstrates significant efficacy against malaria when expressing the pre-erythrocytic malaria antigen Thrombospondin-Related Adhesion Protein fused to a multiple epitope string (ME-TRAP). We tested these vaccines in 7 new 4- and 8- week interval schedules to evaluate safety and immunogenicity of multiple ChAd63 ME-TRAP priming vaccinations (denoted A), multiple MVA ME-TRAP boosts (denoted M) and alternating vectors. All regimens exhibited acceptable reactogenicity and CD8+ T cell immunogenicity was enhanced with a 4-week interval (AM) and with incorporation of additional ChAd63 ME-TRAP vaccination at 4- or 8-weeks (AAM or A_A_M). Induction of TRAP antibodies was comparable between schedules. T cell immunity against the ChAd63 hexon did not affect T cell responses to the vaccine insert, however pre-vaccination ChAd63-specific T cells correlated with reduced TRAP antibodies. Vaccine-induced antibodies against MVA did not affect TRAP antibody induction, and correlated positively with ME-TRAP-specific T cells. This study identifies potentially more effective immunisation regimens to assess in Phase IIa trials and demonstrates a degree of flexibility with the timing of vectored vaccine administration, aiding incorporation into existing vaccination programmes.