bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cisplatin-enriching cancer stem cells confer multidrug resistance in non-small cell lung cancer via enhancing TRIB1/HDAC activity
Authors: Wang Lihui , Liu Xing , Ren Yong , Zhang Jingyuan , Chen Junli , Zhou Wenlong , Guo Wei , Wang Xiaoxuan , Chen Huiping , Li Meng , Yuan Xiangzhong , Zhang Xun , Yang Jingyu , Wu Chunfu 
Published: April 2017

AbstractChemotherapeutic agents are generally used as a frontline therapy for non-small cell lung cancer (NSCLC). However, resistance to chemotherapy arises rapidly in NSCLC, and the reasons for chemotherapy resistance have not been fully determined. Here, we found cisplatin, but not paclitaxel and doxorubicin, induced the enrichment of cancer stem cell (CSC) and conferred multidrug resistance in NSCLC cell lines.In vivostudy confirmed drug-resistant tumors displayed the enhanced expressions of CSC transcription factors. Mechanistically, cisplatin treatment resulted in C/EBP-β-dependent increasing of TRIB1. The crucial role of TRIB1 in cisplatin-induced enrichment of CSC and drug resistance was verified by knockdown TRIB1. Interestingly, cisplatin treatment also contributed to the increasement of HDAC, the interaction of TRIB1 with HDAC, and inactivation of p53. Similarly, the silencing of HDAC led to reduction of cisplatin-induced CSC, and combined knockdown of HDAC and TRIB1 exhibited enhanced effect. Additionally, the combination of HDAC inhibitor and cisplatin showed a reinforced antitumor action in NSCLC cell lines with TRIB1-dependent manner and remarkably shrink tumors in xenograft models. Moreover, cisplatin-treated NSCLC patients with high levels of TRIB1 exhibited a significantly poorer prognosis. Our findings illustrate a novel perspective in the evolution of chemotherapy resistance and provide a promising approach for the treatment of patients with NSCLC.
The suppression of apoptosis by α-herpesvirus
Authors: You Yu , Cheng An-Chun , Wang Ming-Shu , Jia Ren-Yong , Sun Kun-Feng , Yang Qiao , Wu Ying , Zhu Dekang , Chen Shun , Liu Ma-Feng , Zhao Xin-Xin , Chen Xiao-Yue 
Published: April 2017

AbstractApoptosis, an important innate immune mechanism that eliminates pathogen-infected cells, is primarily triggered by two signalling pathways: the death receptor pathway and the mitochondria-mediated pathway. However, many viruses have evolved various strategies to suppress apoptosis by encoding anti-apoptotic factors or regulating apoptotic signalling pathways, which promote viral propagation and evasion of the host defence. During its life cycle, α-herpesvirus utilizes an elegant multifarious anti-apoptotic strategy to suppress programmed cell death. This progress article primarily focuses on the current understanding of the apoptosis-inhibition mechanisms of α-herpesvirus anti-apoptotic genes and their expression products and discusses future directions, including how the anti-apoptotic function of herpesvirus could be targeted therapeutically.
miR-21 ablation and obeticholic acid ameliorate nonalcoholic steatohepatitis in mice
Authors: Rodrigues Pedro M , Afonso Marta B , Simão André L , Carvalho Catarina C , Trindade Alexandre , Duarte António , Borralho Pedro M , Machado Mariana V , Cortez-Pinto Helena , Rodrigues Cecília MP , Castro Rui E 
Published: April 2017

AbstractmicroRNAs were recently suggested to contribute to the pathogenesis of nonalcoholic fatty liver disease (NAFLD), a disease lacking specific pharmacological treatments. In that regard, nuclear receptors are arising as key molecular targets for the treatment of nonalcoholic steatohepatitis (NASH). Here we show that, in a typical model of NASH-associated liver damage, microRNA-21 (miR-21) ablation results in a progressive decrease in steatosis, inflammation and lipoapoptosis, with impairment of fibrosis. In a complementary fast food (FF) diet NASH model, mimicking features of the metabolic syndrome, miR-21 levels increase in both liver and muscle, concomitantly with decreased expression of peroxisome proliferator-activated receptor α (PPARα), a key miR-21 target. Strikingly, miR-21 knockout mice fed the FF diet supplemented with farnesoid X receptor (FXR) agonist obeticholic acid (OCA) display minimal steatosis, inflammation, oxidative stress and cholesterol accumulation. In addition, lipoprotein metabolism was restored, including decreased fatty acid uptake and polyunsaturation, and liver and muscle insulin sensitivity fully reinstated. Finally, the miR-21/PPARα axis was found amplified in liver and muscle biopsies, and in serum, of NAFLD patients, co-substantiating its role in the development of the metabolic syndrome. By unveiling that miR-21 abrogation, together with FXR activation by OCA, significantly improves whole body metabolic parameters in NASH, our results highlight the therapeutic potential of nuclear receptor multi-targeting therapies for NAFLD.
Liver receptor homolog-1 (NR5a2) regulates CD95/Fas ligand transcription and associated T-cell effector functions
Authors: Schwaderer Juliane , Gaiser Ann-Kathrin , Phan Truong San , Delgado M Eugenia , Brunner Thomas 
Published: April 2017

AbstractCD95/Fas ligand (FasL) is a cell death-promoting member of the tumor necrosis factor family with important functions in the regulation of T-cell homeostasis and cytotoxicity. In T cells, FasL expression is tightly regulated on a transcriptional level involving a complex set of different transcription factors. The orphan nuclear receptor liver receptor homolog-1 (LRH-1/NR5a2) is involved in the regulation of development, lipid metabolism and proliferation and is predominantly expressed in epithelial tissues. However, its expression in T lymphocytes has never been reported so far. Based onin silicoanalysis, we identified potential LRH-1 binding sites within theFASLGpromoter. Here, we report that LRH-1 is expressed in primary and secondary lymphatic tissues, as well as in CD4+and CD8+T cells. LRH-1 directly binds to its binding sites in theFASLGpromoter, and thereby drivesFASLGpromoter activity. Mutations in the LRH-1 binding sites reduceFASLGpromoter activity. Pharmacological inhibition of LRH-1 decreases activation-induced FasL mRNA expression, as well as FasL-mediated activation-induced T-cell apoptosis and T-cell cytotoxicity. In a mouse model of Concanavalin A-induced and FasL-mediated hepatitis pharmacological inhibition of LRH-1 resulted in decreased hepatic FasL expression and a significant reduction of liver damage. In summary, these data show for the first time LRH-1 expression in T cells, its role inFASLGtranscription and the potential of pharmacological inhibition of LRH-1 in the treatment of FasL-mediated immunopathologies.
Implantable batteryless device for on-demand and pulsatile insulin administration
Authors: Lee Seung Ho , Lee Young Bin , Kim Byung Hwi , Lee Cheol , Cho Young Min , Kim Se-Na , Park Chun Gwon , Cho Yong-Chan , Choy Young Bin 
Published: April 2017

AbstractMany implantable systems have been designed for long-term, pulsatile delivery of insulin, but the lifetime of these devices is limited by the need for battery replacement and consequent replacement surgery. Here we propose a batteryless, fully implantable insulin pump that can be actuated by a magnetic field. The pump is prepared by simple-assembly of magnets and constituent units and comprises a drug reservoir and actuator equipped with a plunger and barrel, each assembled with a magnet. The plunger moves to noninvasively infuse insulin only when a magnetic field is applied on the exterior surface of the body. Here we show that the dose is easily controlled by varying the number of magnet applications. Also, pump implantation in diabetic rats results in profiles of insulin concentration and decreased blood glucose levels similar to those observed in rats treated with conventional subcutaneous insulin injections.
Gene expression in breast and adipose tissue after 12 months of weight loss and vitamin D supplementation in postmenopausal women
Authors: Mason Caitlin , Wang Lei , Duggan Catherine , Imayama Ikuyo , Thomas Sushma S. , Wang Ching-Yun , Korde Larissa A. , McTiernan Anne 
Published: April 2017

AbstractAdipose tissue is involved in the etiology of postmenopausal breast cancer, possibly through increased sex steroid hormone production, inflammation, and altered adipokines. Vitamin D may affect these pathways but its effect on gene expression in different tissues has not been examined. Within a double-blind, 12-month placebo-controlled randomized trial, we compared 2000 IU/day oral vitamin D3 supplementation (N = 39) vs. placebo (N = 40) on the expression of 5 genes in breast and adipose tissue in overweight/obese postmenopausal women (50–75 years). All participants had serum 25-hydroxyvitamin D (25(OH)D) levels ≥ 10–<32 ng/mL (“insufficient”) and concurrently completed a behavioral weight loss program. Random periareolar fine needle aspiration (RPFNA) and abdominal subcutaneous adipose tissue biopsies were performed at baseline and 12 months. Changes in expression of aromatase (CYP19A1), peroxisome proliferator-activated receptor gamma (PPARG), adiponectin (ADIPOQ), monocyte-chemoattractant protein 1 (MCP-1), and vitamin D receptor (VDR) were analyzed by qRT-PCR. Compared to placebo, 2000 IU vitamin D did not show significant effects on gene expression in breast or adipose tissue. Replete women (i.e., 25(OH)D ≥ 32 ng/mL; N = 17) showed a small decrease in MCP-1 expression compared to an increase among women who remained ‘insufficient’ despite supplementation (N = 12) (Replete:−1.6% vs. Non-replete: 61.2%, p = 0.015) in breast, but not adipose tissue. No statistically significant differences in gene expression were detected according to degree of weight loss. Vitamin D repletion during weight loss may have different effects on gene expression in breast and adipose tissue. Further research on the localized effects of vitamin D is needed to determine its effect on breast cancer risk.
Engineering the quantum states of light in a Kerr-nonlinear resonator by two-photon driving
Authors: Puri Shruti , Boutin Samuel , Blais Alexandre 
Published: April 2017

AbstractPhotonic cat states stored in high-Q resonators show great promise for hardware efficient universal quantum computing. We propose an approach to efficiently prepare such cat states in a Kerr-nonlinear resonator by the use of a two-photon drive. Significantly, we show that this preparation is robust against single-photon loss. An outcome of this observation is that a two-photon drive can eliminate undesirable phase evolution induced by a Kerr nonlinearity. By exploiting the concept of transitionless quantum driving, we moreover demonstrate how non-adiabatic initialization of cat states is possible. Finally, we present a universal set of quantum logical gates that can be performed on the engineered eigenspace of such a two-photon driven resonator and discuss a possible realization using superconducting circuits. The robustness of the engineered subspace to higher-order circuit nonlinearities makes this implementation favorable for scalable quantum computation.
NOD1 modulates IL-10 signalling in human dendritic cells
Authors: Neuper Theresa , Ellwanger Kornelia , Schwarz Harald , Kufer Thomas A. , Duschl Albert , Horejs-Hoeck Jutta 
Published: April 2017

AbstractNOD1 belongs to the family of NOD-like receptors, which is a group of well-characterised, cytosolic pattern-recognition receptors. The best-studied function of NOD-like receptors is their role in generating immediate pro-inflammatory and antimicrobial responses by detecting specific bacterial peptidoglycans or by responding to cellular stress and danger-associated molecules. The present study describes a regulatory, peptidoglycan-independent function of NOD1 in anti-inflammatory immune responses. We report that, in human dendritic cells, NOD1 balances IL-10-induced STAT1 and STAT3 activation by a SOCS2-dependent mechanism, thereby suppressing the tolerogenic dendritic cell phenotype. Based on these findings, we propose that NOD1 contributes to inflammation not only by promoting pro-inflammatory processes, but also by suppressing anti-inflammatory pathways.
Fano resonance with high local field enhancement under azimuthally polarized excitation
Authors: Shang Wuyun , Xiao Fajun , Zhu Weiren , He Hongsen , Premaratne Malin , Mei Ting , Zhao Jianlin 
Published: April 2017

AbstractBeing an enabling technology for applications such as ultrasensitive biosensing and surface enhanced spectroscopy, enormous research interests have been focused on further boosting the local field enhancement at Fano resonance. Here, we demonstrate a plasmonic Fano resonance resulting from the interference between a narrow magnetic dipole mode and a broad electric dipole mode in a split-ring resonator (SRR) coupled to a nanoarc structure. Strikingly, when subjected to an azimuthally polarized beam (APB) excitation, the intensity enhancement becomes more than 60 times larger than that for a linearly polarized beam (LPB). We attribute this intensity enhancement to the improved conversion efficiency between the excitation and magnetic dipole mode along with improved near-field coupling. The APB excited Fano structure is further used as a nanoruler and beam misalignment sensor, due to the high sensitivity of intensity enhancement and scattering spectra to structure irregularities and excitation beam misalignment. Interestingly, we find that, regardless of the presence of structural translations, the proposed structure still maintains over 60 times better intensity enhancement under APB excitation compared to LPB excitation. Moreover, even if the APB excitation is somewhat misaligned, our Fano structure still manages to give a larger intensity enhancement than its counterpart excited by LPB.
Systematic Synergy of Glucose and GLP-1 to Stimulate Insulin Secretion Revealed by Quantitative Phosphoproteomics
Authors: Tang Jia-shu , Li Qing-run , Li Jia-ming , Wu Jia-rui , Zeng Rong 
Published: April 2017

AbstractGLP-1 synergizes with glucose in regulating pancreatic β-cell function, including facilitating β-cell survival and insulin secretion. Though it has been widely accepted that phosphorylation is extremely important in regulating β-cell functions, our knowledge to the global mechanism is still limited. Here we performed a quantitative phosphoproteomics study to systematically present the synergistic regulation of INS-1E cell phosphoproteome mediated by glucose and GLP-1. We generated the largest pancreatic β-cell phosphoproteome by identifying 25,327 accurately localized phosphorylation sites on 5,389 proteins. Our results discovered several novel kinases regulated by glucose, GLP-1 or their synergism, and some of these kinases might act as downstream molecules of GLP-1 mediated PKA signaling cascade. A few phosphosites were regulated by both GLP-1 and glucose alone, and these target proteins were highly related to their biological function on pancreatic β-cells. Finally, we found glucose and GLP-1 executed their synergistic effect at multiple levels, especially at pathway level. Both GLP-1 and glucose participated in regulating every single step of the secretion pathway, and systematically synergized their effects in inducing insulin secretion.
Arsenic metabolism in high altitude modern stromatolites revealed by metagenomic analysis
Authors: Kurth Daniel , Amadio Ariel , Ordoñez Omar F. , Albarracín Virginia H. , Gärtner Wolfgang , Farías María E. 
Published: April 2017

AbstractModern stromatolites thrive only in selected locations in the world. Socompa Lake, located in the Andean plateau at 3570 masl, is one of the numerous extreme Andean microbial ecosystems described over recent years. Extreme environmental conditions include hypersalinity, high UV incidence, and high arsenic content, among others. After Socompa’s stromatolite microbial communities were analysed by metagenomic DNA sequencing, taxonomic classification showed dominance of Proteobacteria, Bacteroidetes and Firmicutes, and a remarkably high number of unclassified sequences. A functional analysis indicated that carbon fixation might occur not only by the Calvin-Benson cycle, but also through alternative pathways such as the reverse TCA cycle, and the reductive acetyl-CoA pathway. Deltaproteobacteria were involved both in sulfate reduction and nitrogen fixation. Significant differences were found when comparing the Socompa stromatolite metagenome to the Shark Bay (Australia) smooth mat metagenome: namely, those involving stress related processes, particularly, arsenic resistance. An in-depth analysis revealed a surprisingly diverse metabolism comprising all known types of As resistance and energy generating pathways. While thearsoperon was the main mechanism, an important abundance ofarsMgenes was observed in selected phyla. The data resulting from this work will prove a cornerstone for further studies on this rare microbial community.
AMPK signaling in the nucleus accumbens core mediates cue-induced reinstatement of cocaine seeking
Authors: Gao Xue-Jiao , Yuan Kai , Cao Lu , Yan Wei , Luo Yi-Xiao , Jian Min , Liu Jian-Feng , Fang Qin , Wang Ji-Shi , Han Ying , Shi Jie , Lu Lin 
Published: April 2017

AbstractRelapse to drug seeking can be caused by exposure to drug-associated cues, provoking drug craving even after prolonged abstinence. Recent studies demonstrated that AMP-activated protein kinase (AMPK) regulates neuronal morphology and membrane excitability in neurons. Here, we investigated the role of AMPK activity in the nucleus accumbens (NAc) in relapse to cocaine seeking. We found that exposure to drug-related cues reinstated cocaine-seeking behavior and increased AMPK and p70s6k phosphorylation in the NAc core but not shell. Augmenting AMPK activity by intra-NAc core infusions of the AMPK activator 5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide (AICAR) or adenovirus expressing constitutively active subunits of AMPK decreased cue-induced reinstatement of cocaine seeking and inhibited the mammalian target of rapamycin complex 1 (mTORC1) and extracellular signal-regulated kinase 1/2 (ERK1/2) pathways. In contrast, inhibition of AMPK activity by intra-NAc core infusions of the AMPK inhibitor compound C or adenovirus expressing dominant-negative subunits of AMPK increased cue-induced reinstatement of cocaine seeking and enhanced mTORC1 and ERK1/2 activity. The regulation of AMPK activity in the NAc shell had no effect on cue-induced cocaine seeking. Altogether, these results indicate that AMPK activity in the NAc core is critical for the cue-induced reinstatement of cocaine seeking, which may be mediated by mTORC1 and ERK1/2 signaling.
Aminoglycosides, but not PTC124 (Ataluren), rescue nonsense mutations in the leptin receptor and in luciferase reporter genes
Authors: Bolze Florian , Mocek Sabine , Zimmermann Anika , Klingenspor Martin 
Published: April 2017

AbstractIn rare cases, monogenetic obesity is caused by nonsense mutations in genes regulating energy balance. A key factor herein is the leptin receptor. Here, we focus on leptin receptor nonsense variants causing obesity, namely the human W31X, murine Y333X and rat Y763X mutations, and explored their susceptibilities to aminoglycoside and PTC124 mediated translational read-through in vitro. In a luciferase based assay, all mutations - when analysed within the mouse receptor - were prone to aminoglycoside mediated nonsense suppression with the highest susceptibility for W31X, followed by Y763X and Y333X. For the latter, the corresponding rodent models appear valuable for in vivo experiments. When W31X was studied in the human receptor, its superior read-through susceptibility – initially observed in the mouse receptor – was eliminated, likely due to the different nucleotide context surrounding the mutation in the two orthologues. The impact of the surrounding context on the read-through opens the possibility to discover novel sequence elements influencing nonsense suppression. As an alternative to toxic aminoglycosides, PTC124 was indicated as a superior nonsense suppressor but inconsistent data concerning its read-through activity are reported. PTC124 failed to rescue W31X as well as different nonsense mutated luciferase reporters, thus, challenging its ability to induce translational read-through.
Entropic uncertainty relations for Markovian and non-Markovian processes under a structured bosonic reservoir
Authors: Wang Dong , Huang Ai-Jun , Hoehn Ross D. , Ming Fei , Sun Wen-Yang , Shi Jia-Dong , Ye Liu , Kais Sabre 
Published: April 2017

AbstractThe uncertainty relation is a fundamental limit in quantum mechanics and is of great importance to quantum information processing as it relates to quantum precision measurement. Due to interactions with the surrounding environment, a quantum system will unavoidably suffer from decoherence. Here, we investigate the dynamic behaviors of the entropic uncertainty relation of an atom-cavity interacting system under a bosonic reservoir during the crossover between Markovian and non-Markovian regimes. Specifically, we explore the dynamic behavior of the entropic uncertainty relation for a pair of incompatible observables under the reservoir-induced atomic decay effect both with and without quantum memory. We find that the uncertainty dramatically depends on both the atom-cavity and the cavity-reservoir interactions, as well as the correlation time, τ, of the structured reservoir. Furthermore, we verify that the uncertainty is anti-correlated with the purity of the state of the observed qubit-system. We also propose a remarkably simple and efficient way to reduce the uncertainty by utilizing quantum weak measurement reversal. Therefore our work offers a new insight into the uncertainty dynamics for multi-component measurements within an open system, and is thus important for quantum precision measurements.
Advantages of Unfair Quantum Ground-State Sampling
Authors: Zhang Brian Hu , Wagenbreth Gene , Martin-Mayor Victor , Hen Itay 
Published: April 2017

AbstractThe debate around the potential superiority of quantum annealers over their classical counterparts has been ongoing since the inception of the field. Recent technological breakthroughs, which have led to the manufacture of experimental prototypes of quantum annealing optimizers with sizes approaching the practical regime, have reignited this discussion. However, the demonstration of quantum annealing speedups remains to this day an elusive albeit coveted goal. We examine the power of quantum annealers to provide a different type of quantum enhancement of practical relevance, namely, their ability to serve as useful samplers from the ground-state manifolds of combinatorial optimization problems. We study, both numerically by simulating stoquastic and non-stoquastic quantum annealing processes, and experimentally, using a prototypical quantum annealing processor, the ability of quantum annealers to sample the ground-states of spin glasses differently than thermal samplers. We demonstrate that (i) quantum annealers sample the ground-state manifolds of spin glasses very differently than thermal optimizers (ii) the nature of the quantum fluctuations driving the annealing process has a decisive effect on the final distribution, and (iii) the experimental quantum annealer samples ground-state manifolds significantly differently than thermal and ideal quantum annealers. We illustrate how quantum annealers may serve as powerful tools when complementing standard sampling algorithms.