bluuebunny/crossref_metadata_2025_split huggingface dataset:
HOPX hypermethylation promotes metastasis via activating SNAIL transcription in nasopharyngeal carcinoma
Authors: Ren Xianyue , Yang Xiaojing , Cheng Bin , Chen Xiaozhong , Zhang Tianpeng , He Qingmei , Li Bin , Li Yingqin , Tang Xinran , Wen Xin , Zhong Qian , Kang Tiebang , Zeng Musheng , Liu Na , Ma Jun 
Published: February 2017

AbstractNasopharyngeal carcinoma (NPC) is characterized by a high rate of local invasion and early distant metastasis. Increasing evidence indicates that epigenetic abnormalities play important roles in NPC development. However, the epigenetic mechanisms underlying NPC metastasis remain unclear. Here we investigate aberrantly methylated transcription factors in NPC tissues, and we identify theHOPhomeoboxHOPXas the most significantly hypermethylated gene. Consistently, we find that HOXP expression is downregulated in NPC tissues and NPC cell lines. Restoring HOPX expression suppresses metastasis and enhances chemosensitivity of NPC cells. These effects are mediated by HOPX-mediated epigenetic silencing ofSNAILtranscription through the enhancement of histone H3K9 deacetylation in theSNAILpromoter. Moreover, we find that patients with high methylation levels ofHOPXexhibit poor clinical outcomes in both the training and validation cohorts. In summary,HOPXacts as a tumour suppressor via the epigenetic regulation ofSNAILtranscription, which provides a novel prognostic biomarker for NPC metastasis and therapeutic target for NPC treatment.
β-arrestin-2 is an essential regulator of pancreatic β-cell function under physiological and pathophysiological conditions
Authors: Zhu Lu , Almaça Joana , Dadi Prasanna K. , Hong Hao , Sakamoto Wataru , Rossi Mario , Lee Regina J. , Vierra Nicholas C. , Lu Huiyan , Cui Yinghong , McMillin Sara M. , Perry Nicole A. , Gurevich Vsevolod V. , Lee Amy , Kuo Bryan , Leapman Richard D. , Matschinsky Franz M. , Doliba Nicolai M. , Urs Nikhil M. , Caron Marc G. , Jacobson David A. , Caicedo Alejandro , Wess Jürgen 
Published: February 2017

Abstractβ-arrestins are critical signalling molecules that regulate many fundamental physiological functions including the maintenance of euglycemia and peripheral insulin sensitivity. Here we show that inactivation of the β-arrestin-2 gene, barr2, in β-cells of adult mice greatly impairs insulin release and glucose tolerance in mice fed with a calorie-rich diet. Both glucose and KCl-induced insulin secretion and calcium responses were profoundly reduced in β-arrestin-2 (barr2) deficient β-cells. In human β-cells, barr2 knockdown abolished glucose-induced insulin secretion. We also show that the presence of barr2 is essential for proper CAMKII function in β-cells. Importantly, overexpression of barr2 in β-cells greatly ameliorates the metabolic deficits displayed by mice consuming a high-fat diet. Thus, our data identify barr2 as an important regulator of β-cell function, which may serve as a new target to improve β-cell function.
Coherent control of quasi-degenerate stationary-like states via multiple resonances
Authors: Luo Yunrong , Hai Kuo , Zou Mingliang , Hai Wenhua 
Published: February 2017

AbstractWe use three bosons held in a depth-tilt combined-modulated double-well to study coherent control of quantum transitions between quasi-degenerate stationary-like states (QDSLSs) with the same quasienergy. Within the high-frequency approximation and for multiple-resonance conditions, we analytically obtain the different QDSLSs including the maximal bipartite entangled states, which enable us to manipulate the transitions between QDSLSs without the observable multiphoton absorption and to simulate a two-qubit system with the considered bosons. The analytical results are confirmed numerically and good agreement is shown. The quantum transitions between QDSLSs can be observed and controlled by adjusting the initial and the final atomic distributions in the currently proposed experimental setup, and possess potential applications in qubit control based on the bipartite entangled states and in engineering quantum dynamics for quantum information processing.
Long noncoding RNA expression signature to predict platinum-based chemotherapeutic sensitivity of ovarian cancer patients
Authors: Liu Rong , Zeng Ying , Zhou Cheng-Fang , Wang Ying , Li Xi , Liu Zhao-Qian , Chen Xiao-Ping , Zhang Wei , Zhou Hong-Hao 
Published: February 2017

AbstractDysregulated long noncoding RNAs (lncRNAs) are potential markers of several tumor prognoses. This study aimed to develop a lncRNA expression signature that can predict chemotherapeutic sensitivity for patients with advanced stage and high-grade serous ovarian cancer (HGS-OvCa) treated with platinum-based chemotherapy. The lncRNA expression profiles of 258 HGS-OvCa patients from The Cancer Genome Atlas were analyzed. Results revealed that an eight-lncRNA signature was significantly associated with chemosensitivity in the multivariate logistic regression model, which can accurately predict the chemosensitivity of patients [Area under curve (AUC) = 0.83]. The association of a chemosensitivity predictor with molecular subtypes indicated the excellent prognosis performance of this marker in differentiated, mesenchymal, and immunoreactive subtypes (AUC > 0.8). The significant correlation between ZFAS1 expression and chemosensitivity was confirmed in 233 HGS-OvCa patients from the Gene Expression Omnibus datasets (GSE9891, GSE63885, and GSE51373). In vitro experiments demonstrated that the ZFAS1 expression was upregulated by cisplatin in A2008, HeyA8, and HeyC2 cell lines. This finding suggested that ZFAS1 may participate in platinum resistance. Therefore, the evaluation of the eight-lncRNA signature may be clinically implicated in the selection of platinum-resistant HGS-OvCa patients. The role of ZFAS1 in platinum resistance should be further investigated.
“Deflecting elastic prism” and unidirectional localisation for waves in chiral elastic systems
Authors: Carta G. , Jones I. S. , Movchan N. V. , Movchan A. B. , Nieves M. J. 
Published: February 2017

AbstractFor the first time, a design of a “deflecting elastic prism” is proposed and implemented for waves in a chiral medium. A novel model of an elastic lattice connected to a non-uniform system of gyroscopic spinners is designed to create a unidirectional wave pattern, which can be diverted by modifying the arrangement of the spinners within the medium. This important feature of the gyro-system is exploited to send a wave from a point of the lattice to any other point in the lattice plane, in such a way that the wave amplitude is not significantly reduced along the path. We envisage that the proposed model could be very useful in physical and engineering applications related to directional control of elastic waves.
Inkjet printed circuits based on ambipolar and p-type carbon nanotube thin-film transistors
Authors: Kim Bongjun , Geier Michael L. , Hersam Mark C. , Dodabalapur Ananth 
Published: February 2017

AbstractAmbipolar and p-type single-walled carbon nanotube (SWCNT) thin-film transistors (TFTs) are reliably integrated into various complementary-like circuits on the same substrate by inkjet printing. We describe the fabrication and characteristics of inverters, ring oscillators, and NAND gates based on complementary-like circuits fabricated with such TFTs as building blocks. We also show that complementary-like circuits have potential use as chemical sensors in ambient conditions since changes to the TFT characteristics of the p-channel TFTs in the circuit alter the overall operating characteristics of the circuit. The use of circuits rather than individual devices as sensors integrates sensing and signal processing functions, thereby simplifying overall system design.
The Calcium-Dependent Switch Helix of L-Plastin Regulates Actin Bundling
Authors: Ishida Hiroaki , Jensen Katharine V. , Woodman Andrew G. , Hyndman M. Eric , Vogel Hans J. 
Published: February 2017

AbstractL-plastin is a calcium-regulated actin-bundling protein that is expressed in cells of hematopoietic origin and in most metastatic cancer cells. These cell types are mobile and require the constant remodeling of their actin cytoskeleton, where L-plastin bundles filamentous actin. The calcium-dependent regulation of the actin-bundling activity of L-plastin is not well understood. We have used NMR spectroscopy to determine the solution structure of the EF-hand calcium-sensor headpiece domain. Unexpectedly, this domain does not bind directly to the four CH-domains of L-plastin. A novel switch helix is present immediately after the calcium-binding region and it binds tightly to the EF-hand motifs in the presence of calcium. We demonstrate that this switch helix plays a major role during actin-bundling. Moreover a peptide that competitively inhibits the association between the EF-hand motifs and the switch helix was shown to deregulate the actin-bundling activity of L-plastin. Overall, these findings may help to develop new drugs that target the L-plastin headpiece and interfere in the metastatic activity of cancer cells.
Sublethal pesticide doses negatively affect survival and the cellular responses in American foulbrood-infected honeybee larvae
Authors: López Javier Hernández , Krainer Sophie , Engert Antonia , Schuehly Wolfgang , Riessberger-Gallé Ulrike , Crailsheim Karl 
Published: February 2017

AbstractDisclosing interactions between pesticides and bee infections is of most interest to understand challenges that pollinators are facing and to which extent bee health is compromised. Here, we address the individual and combined effect that three different pesticides (dimethoate, clothianidin and fluvalinate) and an American foulbrood (AFB) infection have on mortality and the cellular immune response of honeybee larvae. We demonstrate for the first time a synergistic interaction when larvae are exposed to sublethal doses of dimethoate or clothianidin in combination with Paenibacillus larvae, the causative agent of AFB. A significantly higher mortality than the expected sum of the effects of each individual stressor was observed in co-exposed larvae, which was in parallel with a drastic reduction of the total and differential hemocyte counts. Our results underline that characterizing the cellular response of larvae to individual and combined stressors allows unmasking previously undetected sublethal effects of pesticides in colony health.
M48U1 and Tenofovir combination synergistically inhibits HIV infection in activated PBMCs and human cervicovaginal histocultures
Authors: Musumeci Giuseppina , Bon Isabella , Lembo David , Cagno Valeria , Re Maria Carla , Signoretto Caterina , Diani Erica , Lopalco Lucia , Pastori Claudia , Martin Loïc , Ponchel Gilles , Gibellini Davide , Bouchemal Kawthar 
Published: February 2017

AbstractMicrobicides are considered a promising strategy for preventing human immunodeficiency virus (HIV-1) transmission and disease. In this report, we first analyzed the antiviral activity of the miniCD4 M48U1 peptide formulated in hydroxyethylcellulose (HEC) hydrogel in activated peripheral blood mononuclear cells (PBMCs) infected with R5- and X4–tropic HIV-1 strains. The results demonstrate that M48U1 prevented infection by several HIV-1 strains including laboratory strains, and HIV-1 subtype B and C strains isolated from the activated PBMCs of patients. M48U1 also inhibited infection by two HIV-1 transmitted/founder infectious molecular clones (pREJO.c/2864 and pTHRO.c/2626). In addition, M48U1 was administered in association with tenofovir, and these two antiretroviral drugs synergistically inhibited HIV-1 infection. In the next series of experiments, we tested M48U1 alone or in combination with tenofovir in HEC hydrogel with an organ-like structure mimicking human cervicovaginal tissue. We demonstrated a strong antiviral effect in absence of significant tissue toxicity. Together, these results indicate that co-treatment with M48U1 plus tenofovir is an effective antiviral strategy that may be used as a new topical microbicide to prevent HIV-1 transmission.
Two strategies to engineer flexible loops for improved enzyme thermostability
Authors: Yu Haoran , Yan Yihan , Zhang Cheng , Dalby Paul A. 
Published: February 2017

AbstractFlexible sites are potential targets for engineering the stability of enzymes. Nevertheless, the success rate of the rigidifying flexible sites (RFS) strategy is still low due to a limited understanding of how to determine the best mutation candidates. In this study, two parallel strategies were applied to identify mutation candidates within the flexible loops of Escherichia coli transketolase (TK). The first was a “back to consensus mutations” approach, and the second was computational design based on ΔΔG calculations in Rosetta. Forty-nine single variants were generated and characterised experimentally. From these, three single-variants I189H, A282P, D143K were found to be more thermostable than wild-type TK. The combination of A282P with H192P, a variant constructed previously, resulted in the best all-round variant with a 3-fold improved half-life at 60 °C, 5-fold increased specific activity at 65 °C, 1.3-fold improved kcat and a Tm increased by 5 °C above that of wild type. Based on a statistical analysis of the stability changes for all variants, the qualitative prediction accuracy of the Rosetta program reached 65.3%. Both of the two strategies investigated were useful in guiding mutation candidates to flexible loops, and had the potential to be used for other enzymes.
TDtest: easy detection of bacterial tolerance and persistence in clinical isolates by a modified disk-diffusion assay
Authors: Gefen Orit , Chekol Betty , Strahilevitz Jacob , Balaban Nathalie Q. 
Published: February 2017

AbstractAntibiotic tolerance - the ability for prolonged survival under bactericidal treatments - is a potentially clinically significant phenomenon that is commonly overlooked in the clinical microbiology laboratory. Recent in vitro experiments show that high tolerance can evolve under intermittent antibiotic treatments in as little as eight exposures to high doses of antibiotics, suggesting that tolerance may evolve also in patients. However, tests for antibiotic susceptibilities, such as the disk-diffusion assay, evaluate only the concentration at which a bacterial strain stops growing, namely resistance level. High tolerance strains will not be detected using these tests. We present a simple modification of the standard disk-diffusion assay that allows the semi-quantitative evaluation of tolerance levels. This novel method, the “TDtest”, enabled the detection of tolerant and persistent bacteria by promoting the growth of the surviving bacteria in the inhibition zone, once the antibiotic has diffused away. Using the TDtest, we were able to detect different levels of antibiotic tolerance in clinical isolates of E. coli. The TDtest also identified antibiotics that effectively eliminate tolerant bacteria. The additional information on drug susceptibility provided by the TDtest should enable tailoring better treatment regimens for pathogenic bacteria.
ERAMOSA controls lateral branching in snapdragon
Authors: Mizzotti Chiara , Galliani Bianca M. , Dreni Ludovico , Sommer Hans , Bombarely Aureliano , Masiero Simona 
Published: February 2017

AbstractPlant forms display a wide variety of architectures, depending on the number of lateral branches, internode elongation and phyllotaxy. These are in turn determined by the number, the position and the fate of the Axillary Meristems (AMs). Mutants that affect AM determination during the vegetative phase have been isolated in several model plants. Among these genes, the GRAS transcription factorLATERAL SUPPRESSOR (Ls) plays a pivotal role in AM determination during the vegetative phase. Hereby we characterize the phylogenetic orthologue of Ls in Antirrhinum, ERAMOSA (ERA). Our data supported ERA control of AM formation during both the vegetative and the reproductive phase in snapdragon. A phylogenetic analysis combined with an analysis of the synteny of Ls in several species strongly supported the hypothesis that ERA is a phylogenetic orthologue of Ls, although it plays a broader role. During the reproductive phase ERA promotes the establishment of the stem niche at the bract axis but, after the reproductive transition, it is antagonized by the MADS box transcription factor SQUAMOSA (SQUA). Surprisingly double mutantera squaplants display asquaphenotype developing axillary meristems, which can eventually turn into inflorescences or flowers.
Efficient electrochemical remediation of microcystin-LR in tap water using designer TiO2@carbon electrodes
Authors: Sanz Lobón Germán , Yepez Alfonso , Garcia Luane Ferreira , Morais Ruiter Lima , Vaz Boniek Gontijo , Carvalho Veronica Vale , de Oliveira Gisele Augusto Rodrigues , Luque Rafael , Gil Eric de Souza 
Published: February 2017

AbstractMicrocystin-leucine arginine (MC-LR) is the most abundant and toxic secondary metabolite produced by freshwater cyanobacteria. This toxin has a high potential hazard health due to potential interactions with liver, kidney and the nervous system. The aim of this work was the design of a simple and environmentally friendly electrochemical system based on highly efficient nanostructured electrodes for the removal of MC-LR in tap water. Titania nanoparticles were deposited on carbon (graphite) under a simple and efficient microwave assisted approach for the design of the electrode, further utilized in the electrochemical remediation assays. Parameters including the applied voltage, time of removal and pH (natural tap water or alkaline condition) were investigated in the process, with results pointing to a high removal efficiency for MC-LR (60% in tap water and 90% in alkaline media experiments, under optimized conditions).
Role of thermal physiology and bioenergetics on adaptation in tree shrew (Tupaia belangeri): the experiment test
Authors: Zhang Lin , Yang Fang , Wang Zheng-kun , Zhu Wan-long 
Published: February 2017

AbstractAmbient conditions, as temperature and photoperiod, play a key role in animals’ physiology and behaviors. To test the hypothesis that the maximum thermal physiological and bioenergetics tolerances are induced by extreme environments in Tupaia belangeri. We integrated the acclimatized and acclimated data in several physiological, hormonal, and biochemical markers of thermogenic capacity and bioenergetics in T. belangeri. Results showed that T. belangeri increased body mass, thermogenesis capacity, protein contents and cytochrome c oxidase (COX) activity of liver and brown adipose tissue in winter-like environments, which indicated that temperature was the primary signal for T. belangeri to regulate several physiological capacities. The associated photoperiod signal also elevated the physiological capacities. The regulations of critical physiological traits play a primary role in meeting the survival challenges of winter-like condition in T. belangeri. Together, to cope with cold, leptin may play a potential role in thermogenesis and body mass regulation, as this hormonal signal is associated with other hormones. The strategies of thermal physiology and bioenergetics differs between typical Palearctic species and the local species. However, the maximum thermal physiology and bioenergetic tolerance maybe is an important strategy to cope with winter-like condition of T. belangeri.
Induction of Bex genes by curcumin is associated with apoptosis and activation of p53 in N2a neuroblastoma cells
Authors: Sidhar Himakshi , Giri Ranjit K. 
Published: February 2017

AbstractBrain expressed X-linked (Bex) genes are newer group of pro-apoptotic genes. Role of any Bex gene in neuroblastoma and Bex4 and Bex6 in any cancer is completely unknown. Re-expression of all endogenous Bex genes by any nutraceutical is also unknown. Therefore, we investigated the induction of all endogenous Bex genes and associated mechanisms by curcumin using N2a, an aggressive neuroblastoma cell line. Curcumin induced all endogenous Bex genes prior to apoptosis in N2a cells in a dose- and time-dependent manner. Wortmannin (PI-3Kinases inhibitor), SP600125 (JNK inhibitor) and pifithrin-α (p53 inhibitor) abrogated curcumin-mediated induction of Bex genes. Inhibition of curcumin-mediated induction of Bex genes by pifithrin-α also inhibited N2a cells apoptosis suggesting, a direct role of Bex genes in N2a cells apoptosis and involvement of p53 in Bex genes induction. Curcumin treatment activated p53 through hyperphosphorylation at serine 15 before Bex genes induction indicating Bex genes are novel downstream targets of p53. Collectively, curcumin, a safe nutraceutical has the potential to induce all endogenous Bex genes to harness their anti-cancer properties in neuroblastoma cells. Re-expression of Bex genes by curcumin acts as tumor suppressors and may provide alternate strategy to treat neuroblastomas and other cancers with silenced Bex genes.
Hydrogen-enabled microstructure and fatigue strength engineering of titanium alloys
Authors: Paramore James D. , Fang Zhigang Zak , Dunstan Matthew , Sun Pei , Butler Brady G. 
Published: February 2017

AbstractTraditionally, titanium alloys with satisfactory mechanical properties can only be produced via energy-intensive and costly wrought processes, while titanium alloys produced using low-cost powder metallurgy methods consistently result in inferior mechanical properties, especially low fatigue strength. Herein, we demonstrate a new microstructural engineering approach for producing low-cost titanium alloys with exceptional fatigue strength via the hydrogen sintering and phase transformation (HSPT) process. The high fatigue strength presented in this work is achieved by creating wrought-like microstructures without resorting to wrought processing. This is accomplished by generating an ultrafine-grained as-sintered microstructure through hydrogen-enabled phase transformations, facilitating the subsequent creation of fatigue-resistant microstructures via simple heat treatments. The exceptional strength, ductility, and fatigue performance reported in this paper are a breakthrough in the field of low-cost titanium processing.
Targeted nanoparticles encapsulating (−)-epigallocatechin-3-gallate for prostate cancer prevention and therapy
Authors: Sanna Vanna , Singh Chandra K. , Jashari Rahime , Adhami Vaqar M. , Chamcheu Jean Christopher , Rady Islam , Sechi Mario , Mukhtar Hasan , Siddiqui Imtiaz A. 
Published: February 2017

AbstractEarlier we introduced the concept of ‘nanochemoprevention’ i.e. the use of nanotechnology to improve the outcome of cancer chemoprevention. Here, we extended our work and developed polymeric EGCG-encapsulated nanoparticles (NPs) targeted with small molecular entities, able to bind to prostate specific membrane antigen (PSMA), a transmembrane protein that is overexpressed in prostate cancer (PCa), and evaluated their efficacy in preclinical studies. First, we performed a molecular recognition of DCL- and AG-PEGylation on ligand binding on PSMA active site. Next, the biocompatible polymers PLGA-PEG-A were synthesized and used as base to conjugate DCL or AG to obtain the respective copolymers, needed for the preparation of targeted NPs. The resulting EGCG encapsulating NPs led to an enhanced anti-proliferative activity in PCa cell lines compared to the free EGCG. The behavior of EGCG encapsulated in NPs in modulating apoptosis and cell-cycle, was also determined. Then, in vivo experiments, in mouse xenograft model of prostatic tumor, using EGCG-loaded NPs, with a model of targeted nanosystems, were conducted. The obtained data supported our hypothesis of target-specific enhanced bioavailability and limited unwanted toxicity, thus leading to a significant potential for probable clinical outcome.