bluuebunny/crossref_metadata_2025_split huggingface dataset:
Homocysteine activates autophagy by inhibition of CFTR expression via interaction between DNA methylation and H3K27me3 in mouse liver
Authors: Yang Anning , Jiao Yun , Yang Songhao , Deng Mei , Yang Xiaoling , Mao Caiyan , Sun Yue , Ding Ning , Li Nan , Zhang Minghao , Jin Shaoju , Zhang Huiping , Jiang Yideng 
Published: February 2018

AbstractElevated homocysteine (Hcy) levels have been reported to be involved in liver injury, and autophagy plays an important role in normal hepatic physiology and pathophysiology, but the mechanism underlying Hcy regulated autophagy is currently unknown. In this study, CBS+/- mice were fed with regular diet for 12 weeks to establish a hyperhomocysteinemia (HHcy) model and HL-7702 cells were treated with Hcy, we found that Hcy increases autophagy and aggravates liver injury by downregulation of cystic fibrosis transmembrane conductance regulator (CFTR) expression in vivo and in vitro. Overexpression of CFTR inhibited the formation of autophagosomes and the expression of autophagy-related proteins BECN1, LC3-II/I and Atg12, while the expression of p62 increased in Hcy-treated hepatocytes and CBS+/- mice injected with lentivirus expressing CFTR. Further study showed that CFTR expression is regulated by the interaction of DNA methyltransferase 1 (DNMT1) and enhancer of zeste homolog 2 (EZH2), which, respectively, regulate DNA methylation and histone H3 lysine 27 trimethylation (H3K27me3). In conclusion, our study showed that Hcy activates autophagy by inhibition of CFTR expression via interaction between H3K27me3 and DNA methylation in the mouse liver. These findings provide new insight into the mechanism of Hcy-induced autophagy in liver injury.
MicroRNA-1253 suppresses cell proliferation and invasion of non-small-cell lung carcinoma by targeting WNT5A
Authors: Liu Meiyue , Zhang Yue , Zhang Jie , Cai Haifeng , Zhang Chao , Yang Zhao , Niu Yi , Wang Huan , Wei Xiaomei , Wang Wei , Gao Peng , Li Hongmin , Zhang Jinghua , Sun Guogui 
Published: February 2018

AbstractMicroRNAs (miRNA) are a class of small, noncoding RNA molecules that regulate the expression of target genes. miRNA dysregulation is involved in carcinogenesis and tumor progression. In this study, we identified microRNA-1253 (miR-1253) as being significantly down-regulated in non-small-cell lung carcinoma (NSCLC) tissues and associated with advanced clinical stage, lymph node metastasis, and poor survival. The enhanced expression of miR-1253 significantly inhibited the proliferation, migration, and invasion of NSCLC cells in vitro. Bioinformatics analyses showed that miR-1253 directly targeted WNT5A (long isoform), which was confirmed using the dual-luciferase reporter assay. The inhibitory effects of miR-1253 on the growth and metastasis of NSCLC cells were attenuated and phenocopied by WNT5A (long) overexpression and knockdown, respectively. Consistent with the in vitro results, subcutaneous tumor and metastatic NSCLC mouse models showed that miR-1253 functions as a potent suppressor of NSCLC in vivo. Taken together, our findings indicated that miR-1253 inhibited the proliferation and metastasis of NSCLC cells by targeting WNT5A (long isoform) and provided new evidence of miR-1253 as a potential therapeutic target in NSCLC.
Osteopontin promotes metastasis of intrahepatic cholangiocarcinoma through recruiting MAPK1 and mediating Ser675 phosphorylation of β-Catenin
Authors: Zheng Yan , Zhou Chuang , Yu Xin-Xin , Wu Chao , Jia Hu-Liang , Gao Xiao-Mei , Yang Ji-Meng , Wang Chao-Qun , Luo Qin , Zhu Ying , Zhang Yu , Wei Jin-Wang , Sheng Yuan-Yuan , Dong Qiong-Zhu , Qin Lun-Xiu 
Published: February 2018

AbstractThe incidence and mortality of intrahepatic cholangiocarcinoma (ICC) are increasing worldwide in recent decades. Osteopontin (OPN) plays an important role in cancer metastasis, but its functional mechanism in ICC is not clear yet. In this study, we found that OPN level was elevated both in plasma and tumor tissues of ICC patients, which was closely related to a shorter overall survival (OS) and high probability of tumor relapse after curative resection. The gain- and loss-of-function studies determined that OPN could promote ICC growth and metastasis. OPN selectively interacted with β-Catenin and knockdown of β-Catenin abrogated the effects induced by OPN. OPN recruited MAPK1 and activated MEK–MAPK1 pathway to mediate the S675 phosphorylation of β-Catenin and nucleus accumulation, which induced the activation of Wnt signaling. Moreover, a significant correlation between OPN and β-Catenin was found in ICC tissues. OPN, β-Catenin, and their combination were independent prognostic indicator for ICC patients. In conclusion, OPN promotes ICC progression through recruiting MAPK1 and activating the Wnt/β-Catenin pathway and can serve as a novel prognostic marker and therapeutic target for ICC.
Antitumor activity of EGFR-specific CAR T cells against non-small-cell lung cancer cells in vitro and in mice
Authors: Li He , Huang Yao , Jiang Du-Qing , Cui Lian-Zhen , He Zhou , Wang Chao , Zhang Zhi-Wei , Zhu Hai-Li , Ding Yong-Mei , Li Lin-Fang , Li Qiang , Jin Hua-Jun , Qian Qi-Jun 
Published: February 2018

AbstractEffective control of non-small-cell lung cancer (NSCLC) remains clinically challenging, especially during advanced stages of the disease. This study developed an adoptive T-cell treatment through expression of a chimeric antigen receptor (CAR) to target human epidermal growth factor receptor (EGFR) in NSCLC. We optimized the non-viral piggyBac transposon system to engineer human T cells for the expression of EGFR-CAR, consisting of EGFR scFv, transmembrane domain, and intracellular 4-1BB-CD3ζ signaling domains. The modified CAR T cells exhibited expansion capability and anticancer efficacy in a time- and antigen-dependent manner in vitro as well as regression of EGFR-positive human lung cancer xenografts in vivo. EGFR-CAR T therapy is a promising strategy to improve the efficacy and potency of the adoptive immunotherapy in NSCLC. Moreover, EGFR-CAR T therapy could become a clinical application for NSCLC patients in the future.
The binding landscape of a partially-selective isopeptidase inhibitor with potent pro-death activity, based on the bis(arylidene)cyclohexanone scaffold
Authors: Ciotti Sonia , Sgarra Riccardo , Sgorbissa Andrea , Penzo Carlotta , Tomasella Andrea , Casarsa Federico , Benedetti Fabio , Berti Federico , Manfioletti Guidalberto , Brancolini Claudio 
Published: February 2018

AbstractDiaryldienone derivatives with accessible β-carbons show strong anti-neoplastic properties, related to their ability to make covalent adducts with free thiols by Michael addition, and low toxicity in vivo. Accumulation of poly-ubiquitylated proteins, activation of the unfolded protein response (UPR) and induction of cell death are universal hallmarks of their activities. These compounds have been characterized as inhibitors of isopeptidases, a family of cysteine-proteases, which de-conjugate ubiquitin and ubiquitin-like proteins from their targets. However, it is unclear whether they can also react with additional proteins. In this work, we utilized the biotin-conjugated diaryldienone-derivative named 2c, as a bait to purify novel cellular targets of these small molecules. Proteomic analyses have unveiled that, in addition to isopeptidases, these inhibitors can form stable covalent adducts with different intracellular proteins, thus potentially impacting on multiple functions of the cells, from cytoskeletal organization to metabolism. These widespread activities can explain the ability of diaryldienone derivatives to efficiently trigger different cell death pathways.
Detecting RNA base methylations in single cells by in situ hybridization
Authors: Ranasinghe Rohan T. , Challand Martin R. , Ganzinger Kristina A. , Lewis Benjamin W. , Softley Charlotte , Schmied Wolfgang H. , Horrocks Mathew H. , Shivji Nadia , Chin Jason W. , Spencer James , Klenerman David 
Published: February 2018

AbstractMethylated bases in tRNA, rRNA and mRNA control a variety of cellular processes, including protein synthesis, antimicrobial resistance and gene expression. Currently, bulk methods that report the average methylation state of ~104–107 cells are used to detect these modifications, obscuring potentially important biological information. Here, we use in situ hybridization of Molecular Beacons for single-cell detection of three methylations (m62A, m1G and m3U) that destabilize Watson–Crick base pairs. Our method—methylation-sensitive RNA fluorescence in situ hybridization—detects single methylations of rRNA, quantifies antibiotic-resistant bacteria in mixtures of cells and simultaneously detects multiple methylations using multicolor fluorescence imaging.
Toward a consistent modeling framework to assess multi-sectoral climate impacts
Authors: Monier Erwan , Paltsev Sergey , Sokolov Andrei , Chen Y.-H. Henry , Gao Xiang , Ejaz Qudsia , Couzo Evan , Schlosser C. Adam , Dutkiewicz Stephanie , Fant Charles , Scott Jeffery , Kicklighter David , Morris Jennifer , Jacoby Henry , Prinn Ronald , Haigh Martin 
Published: February 2018

AbstractEfforts to estimate the physical and economic impacts of future climate change face substantial challenges. To enrich the currently popular approaches to impact analysis—which involve evaluation of a damage function or multi-model comparisons based on a limited number of standardized scenarios—we propose integrating a geospatially resolved physical representation of impacts into a coupled human-Earth system modeling framework. Large internationally coordinated exercises cannot easily respond to new policy targets and the implementation of standard scenarios across models, institutions and research communities can yield inconsistent estimates. Here, we argue for a shift toward the use of a self-consistent integrated modeling framework to assess climate impacts, and discuss ways the integrated assessment modeling community can move in this direction. We then demonstrate the capabilities of such a modeling framework by conducting a multi-sectoral assessment of climate impacts under a range of consistent and integrated economic and climate scenarios that are responsive to new policies and business expectations.
Conductance quantization suppression in the quantum Hall regime
Authors: Caridad José M. , Power Stephen R. , Lotz Mikkel R. , Shylau Artsem A. , Thomsen Joachim D. , Gammelgaard Lene , Booth Timothy J. , Jauho Antti-Pekka , Bøggild Peter 
Published: February 2018

AbstractConductance quantization is the quintessential feature of electronic transport in non-interacting mesoscopic systems. This phenomenon is observed in quasi one-dimensional conductors at zero magnetic field B, and the formation of edge states at finite magnetic fields results in wider conductance plateaus within the quantum Hall regime. Electrostatic interactions can change this picture qualitatively. At finite B, screening mechanisms in narrow, gated ballistic conductors are predicted to give rise to an increase in conductance and a suppression of quantization due to the appearance of additional conduction channels. Despite being a universal effect, this regime has proven experimentally elusive because of difficulties in realizing one-dimensional systems with sufficiently hard-walled, disorder-free confinement. Here, we experimentally demonstrate the suppression of conductance quantization within the quantum Hall regime for graphene nanoconstrictions with low edge roughness. Our findings may have profound impact on fundamental studies of quantum transport in finite-size, two-dimensional crystals with low disorder.
Dissection and function of autoimmunity-associated TNFAIP3 (A20) gene enhancers in humanized mouse models
Authors: Sokhi Upneet K. , Liber Mark P. , Frye Laura , Park Sungho , Kang Kyuho , Pannellini Tania , Zhao Baohong , Norinsky Rada , Ivashkiv Lionel B. , Gong Shiaoching 
Published: February 2018

AbstractEnhancers regulate gene expression and have been linked with disease pathogenesis. Little is known about enhancers that regulate human disease-associated genes in primary cells relevant for pathogenesis. Here we use BAC transgenics and genome editing to dissect, in vivo and in primary immune cells, enhancers that regulate human TNFAIP3, which encodes A20 and is linked with autoimmune diseases. A20 expression is dependent on a topologically associating subdomain (sub-TAD) that harbors four enhancers, while another >20 enhancers in the A20 locus are redundant. This sub-TAD contains cell- and activation-specific enhancers, including an enhancer (termed TT>A) harboring a proposed causal SLE-associated SNV. Deletion of the sub-TAD or the TT>A enhancer results in enhanced inflammatory responses, autoantibody production, and inflammatory arthritis, thus establishing functional importance in vivo and linking enhancers with a specific disease phenotype. These findings provide insights into enhancers that regulate human A20 expression to prevent inflammatory pathology and autoimmunity.
A defensin-like protein drives cadmium efflux and allocation in rice
Authors: Luo Jin-Song , Huang Jing , Zeng Da-Li , Peng Jia-Shi , Zhang Guo-Bin , Ma Hai-Ling , Guan Yuan , Yi Hong-Ying , Fu Yan-Lei , Han Bin , Lin Hong-Xuan , Qian Qian , Gong Ji-Ming 
Published: February 2018

AbstractPollution by heavy metals limits the area of land available for cultivation of food crops. A potential solution to this problem might lie in the molecular breeding of food crops for phytoremediation that accumulate toxic metals in straw while producing safe and nutritious grains. Here, we identify a rice quantitative trait locus we name cadmium (Cd) accumulation in leaf 1 (CAL1), which encodes a defensin-like protein. CAL1 is expressed preferentially in root exodermis and xylem parenchyma cells. We provide evidence that CAL1 acts by chelating Cd in the cytosol and facilitating Cd secretion to extracellular spaces, hence lowering cytosolic Cd concentration while driving long-distance Cd transport via xylem vessels. CAL1 does not appear to affect Cd accumulation in rice grains or the accumulation of other essential metals, thus providing an efficient molecular tool to breed dual-function rice varieties that produce safe grains while remediating paddy soils.
Demonstration of Einstein–Podolsky–Rosen steering with enhanced subchannel discrimination
Authors: Sun Kai , Ye Xiang-Jun , Xiao Ya , Xu Xiao-Ye , Wu Yu-Chun , Xu Jin-Shi , Chen Jing-Ling , Li Chuan-Feng , Guo Guang-Can 
Published: February 2018

AbstractEinstein–Podolsky–Rosen (EPR) steering describes a quantum nonlocal phenomenon in which one party can nonlocally affect the other’s state through local measurements. It reveals an additional concept of quantum non-locality, which stands between quantum entanglement and Bell nonlocality. Recently, a quantum information task named as subchannel discrimination (SD) provides a necessary and sufficient characterization of EPR steering. The success probability of SD using steerable states is higher than using any unsteerable states, even when they are entangled. However, the detailed construction of such subchannels and the experimental realization of the corresponding task are still technologically challenging. In this work, we designed a feasible collection of subchannels for a quantum channel and experimentally demonstrated the corresponding SD task where the probabilities of correct discrimination are clearly enhanced by exploiting steerable states. Our results provide a concrete example to operationally demonstrate EPR steering and shine a new light on the potential application of EPR steering.
Integrated-optics heralded controlled-NOT gate for polarization-encoded qubits
Authors: Zeuner Jonas , Sharma Aditya N. , Tillmann Max , Heilmann René , Gräfe Markus , Moqanaki Amir , Szameit Alexander , Walther Philip 
Published: February 2018

AbstractRecent progress in integrated-optics technology has made photonics a promising platform for quantum networks and quantum computation protocols. Integrated optical circuits are characterized by small device footprints and unrivalled intrinsic interferometric stability. Here, we take advantage of femtosecond-laser-written waveguides’ ability to process polarization-encoded qubits and present an implementation of a heralded controlled-NOT gate on chip. We evaluate the gate performance in the computational basis and a superposition basis, showing that the gate can create polarization entanglement between two photons. Transmission through the integrated device is optimized using thermally expanded core fibers and adiabatically reduced mode-field diameters at the waveguide facets. This demonstration underlines the feasibility of integrated quantum gates for all-optical quantum networks and quantum repeaters.
A meta-analysis of diffusion tensor imaging of substantia nigra in patients with Parkinson’s disease
Authors: Deng Xiao-Yan , Wang Li , Yang Ting-Ting , Li Rui , Yu Gang 
Published: February 2018

AbstractParkinson’s disease (PD) is a common neurodegenerative disease characterized by severe, selective loss of pigmented neurons in the substantial nigra (SN). Previous studies have indicated that such loss could be detected by diffusion tensor imaging (DTI). Here, we try to consolidate current DTI data to both quantitatively determine the imaging changes in SN, as well as explore the potential use of DTI for PD diagnosis. Fourteen research articles are included in this meta-analysis, each obtained by searching PubMed, EMBASE, or Cochrane library database dated until July 2017. The articles contain 14 trials with 298 total PD patients and 283 healthy controls (HCs). The results show not only significantly lower FA values of SN in PD compared to that of HCs (WMD = −0.02, 95% CI = [−0.03, −0.02], p < 0.00001), but also a significantly higher MD in PD compared to HCs (WMD = 0.05, 95% CI = [0.03, 0.07], P < 0.0001). This indicates that the sharp difference detected between PD patients and HCs can be detected by DTI. By further analyzing the heterogeneity, we found that FA measurement of SN could be potentially used as a surrogate, noninvasive diagnostic marker toward PD diagnosis.
Mammalian Cells Undergo Endoreduplication in Response to Lactic Acidosis
Authors: Tan Zhihao , Chu De Zhi Valerie , Chan Yong Jie Andrew , Lu Yi Ena , Rancati Giulia 
Published: February 2018

AbstractPolyploidization, a common event during the evolution of different tumours, has been proposed to confer selective advantages to tumour cells by increasing the occurrence of mutations promoting cancer progression and by conferring chemotherapy resistance. While conditions leading to polyploidy in cancer cells have been described, a general mechanism explaining the incidence of this karyotypic change in tumours is still missing. In this study, we tested whether a widespread tumour microenvironmental condition, low pH, could induce polyploidization in mammalian cells. We found that an acidic microenvironment, in the range of what is commonly observed in tumours, together with the addition of lactic acid, induced polyploidization in transformed and non-transformed human cell lines in vitro. In addition, we provide evidence that polyploidization was mainly driven through the process of endoreduplication, i.e. the complete skipping of mitosis in-between two S-phases. These findings suggest that acidic environments, which characterize solid tumours, are a plausible path leading to polyploidization of cancer cells.
Ultrasensitive optical biosensor for detection of miRNA-155 using positively charged Au nanoparticles
Authors: Hakimian Fatemeh , Ghourchian Hedayatollah , Hashemi Azam sadat , Arastoo Mohammad Reza , Behnam Rad Mohammad 
Published: February 2018

AbstractAn ultrasensitive optical biosensor for microRNA-155 (miR-155) was developed to diagnose breast cancer at early stages. At first, the probe DNA covalently bind to the negatively charged gold nanoparticles (citrate-capped AuNPs). Then, the target miR-155 electrostatically adsorb onto the positively charged gold nanoparticles (polyethylenimine-capped AuNP) surface. Finally, by mixing citrate-capped AuNP/probe and polyethylenimine-capped AuNP/miR-155, hybridization occurs and the optical signal of the mixture give a measure to quantify the miR-155 content. The proposed biosensor is able to specify 3-base-pair mismatches and genomic DNA from target miR-155. The novelty of this biosensor is in its ability to trap the label-free target by its branched positively charged polyethylenimine. This method increases loading the target on the polyethylenimine-capped AuNPs’ surface. So, proposed sensor enables miR-155 detection at very low concentrations with the detection limit of 100 aM and a wide linear range from 100 aM to 100 fM.
Panton–Valentine Leukocidin Colocalizes with Retinal Ganglion and Amacrine Cells and Activates Glial Reactions and Microglial Apoptosis
Authors: Liu XuanLi , Heitz Pauline , Roux Michel , Keller Daniel , Bourcier Tristan , Sauer Arnaud , Prévost Gilles , Gaucher David 
Published: February 2018

AbstractExperimental models have established Panton–Valentine leukocidin (PVL) as a potential critical virulence factor during Staphylococcus aureus endophthalmitis. In the present study, we aimed to identify retinal cell targets for PVL and to analyze early retinal changes during infection. After the intravitreous injection of PVL, adult rabbits were euthanized at different time points (30 min, 1, 2, 4 and 8 h). PVL location in the retina, expression of its binding receptor C5a receptor (C5aR), and changes in Müller and microglial cells were analyzed using immunohistochemistry, Western blotting and RT-qPCR. In this model of PVL eye intoxication, only retinal ganglion cells (RGCs) expressed C5aR, and PVL was identified on the surface of two kinds of retinal neural cells. PVL-linked fluorescence increased in RGCs over time, reaching 98% of all RGCs 2 h after PVL injection. However, displaced amacrine cells (DACs) transiently colocalized with PVL. Müller and microglial cells were increasingly activated after injection over time. IL-6 expression in retina increased and some microglial cells underwent apoptosis 4 h and 8 h after PVL infection, probably because of abnormal nitrotyrosine production in the retina.
Genetic and morphological support for possible sympatric origin of fish from subterranean habitats
Authors: Hashemzadeh Segherloo Iraj , Normandeau Eric , Benestan Laura , Rougeux Clément , Coté Guillaume , Moore Jean-Sébastien , Ghaedrahmati NabiAllah , Abdoli Asghar , Bernatchez Louis 
Published: February 2018

AbstractTwo blind Iran cave barbs, Garra typhlops and Garra lorestanensis, exist in sympatry in a single subterranean habitat, raising the hypothesis that they may represent a case of sympatric speciation following a colonization event. Their different mental disc forms have prompted some authors to propose the alternative hypothesis of two separate colonization events. In this study, we analysed a genome-wide panel of 11,257 SNPs genotyped by means of genotyping-by-sequencing combined with mitochondrial cytochrome c oxidase sub-unit I sequence data, field observations and morphological traits to test these two hypotheses. Field data suggest some degree of ecological divergence despite some possible niche overlap such that hybridization is possible. According to both nuclear and mtDNA data, the cave barb species are monophyletic with close phylogenetic relationships with Garra gymnothorax from the Karun-Dez and Karkheh river basins. The historical demography analysis revealed that a model of Isolation-with-Migration (IM) best fitted the data, therefore better supporting a scenario of sympatric origin than that of allopatric isolation followed by secondary contact. Overall, our results offer stronger support to the hypothesis that speciation in the subterranean habitat could have occurred in sympatry following a colonization event from the Karun-Dez-Karkheh basins in the Zagros Mountains of Iran.