bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of FOXM1 as a therapeutic target in B-cell lineage acute lymphoblastic leukaemia
Authors: Buchner Maike , Park Eugene , Geng Huimin , Klemm Lars , Flach Johanna , Passegué Emmanuelle , Schjerven Hilde , Melnick Ari , Paietta Elisabeth , Kopanja Dragana , Raychaudhuri Pradip , Müschen Markus 
Published: March 2015

AbstractDespite recent advances in the cure rate of acute lymphoblastic leukaemia (ALL), the prognosis for patients with relapsed ALL remains poor. Here we identify FOXM1 as a candidate responsible for an aggressive clinical course. We show that FOXM1 levels peak at the pre-B-cell receptor checkpoint but are dispensable for normal B-cell development. Compared with normal B-cell populations, FOXM1 levels are 2- to 60-fold higher in ALL cells and are predictive of poor outcome in ALL patients. FOXM1 is negatively regulated by FOXO3A, supports cell survival, drug resistance, colony formation and proliferation in vitro, and promotes leukemogenesis in vivo. Two complementary approaches of pharmacological FOXM1 inhibition—(i) FOXM1 transcriptional inactivation using the thiazole antibiotic thiostrepton and (ii) an FOXM1 inhibiting ARF-derived peptide—recapitulate the findings of genetic FOXM1 deletion. Taken together, our data identify FOXM1 as a novel therapeutic target, and demonstrate feasibility of FOXM1 inhibition in ALL.
Neutral particle mass spectrometry with nanomechanical systems
Authors: Sage Eric , Brenac Ariel , Alava Thomas , Morel Robert , Dupré Cécilia , Hanay Mehmet Selim , Roukes Michael L. , Duraffourg Laurent , Masselon Christophe , Hentz Sébastien 
Published: March 2015

AbstractCurrent approaches to mass spectrometry (MS) require ionization of the analytes of interest. For high-mass species, the resulting charge state distribution can be complex and difficult to interpret correctly. Here, using a setup comprising both conventional time-of-flight MS (TOF-MS) and nano-electromechanical systems-based MS (NEMS-MS) in situ, we show directly that NEMS-MS analysis is insensitive to charge state: the spectrum consists of a single peak whatever the species’ charge state, making it significantly clearer than existing MS analysis. In subsequent tests, all the charged particles are electrostatically removed from the beam, and unlike TOF-MS, NEMS-MS can still measure masses. This demonstrates the possibility to measure mass spectra for neutral particles. Thus, it is possible to envisage MS-based studies of analytes that are incompatible with current ionization techniques and the way is now open for the development of cutting-edge system architectures with unique analytical capability.
Supramolecular synergy in the boundary lubrication of synovial joints
Authors: Seror Jasmine , Zhu Linyi , Goldberg Ronit , Day Anthony J. , Klein Jacob 
Published: March 2015

AbstractHyaluronan, lubricin and phospholipids, molecules ubiquitous in synovial joints, such as hips and knees, have separately been invoked as the lubricants responsible for the remarkable lubrication of articular cartilage; but alone, these molecules cannot explain the extremely low friction at the high pressures of such joints. We find that surface-anchored hyaluronan molecules complex synergistically with phosphatidylcholine lipids present in joints to form a boundary lubricating layer, which, with coefficient of friction μ≈0.001 at pressures to over 100 atm, has a frictional behaviour resembling that of articular cartilage in the major joints. Our findings point to a scenario where each of the molecules has a different role but must act together with the others: hyaluronan, anchored at the outer surface of articular cartilage by lubricin molecules, complexes with joint phosphatidylcholines to provide the extreme lubrication of synovial joints via the hydration–lubrication mechanism.
Meta-analyses of gene methylation and smoking behavior in non-small cell lung cancer patients
Authors: Huang Tao , Chen Xiaoying , Hong Qingxiao , Deng Zaichun , Ma Hongying , Xin Yanfei , Fang Yong , Ye Huadan , Wang Rujie , Zhang Cheng , Ye Meng , Duan Shiwei 
Published: March 2015

AbstractAberrant DNA methylation can be a potential genetic mechanism in non-small cell lung cancer (NSCLC). However, inconsistent findings existed among the recent association studies between cigarette smoking and gene methylation in lung cancer. The purpose of our meta-analysis was to evaluate the role of gene methylation in the smoking behavior of NSCLC patients. A total of 116 genes were obtained from 97 eligible publications in the current meta-analyses. Our results showed that 7 hypermethylated genes (including CDKN2A, RASSF1, MGMT, RARB, DAPK, WIF1 and FHIT) were significantly associated with the smoking behavior in NSCLC patients. The further population-based subgroup meta-analyses showed that the CDKN2A hypermethylation was significantly associated with cigarette smoking in Japanese, Chinese and Americans. In contrast, a significant association of RARB hypermethylation and smoking behavior was only detected in Chinese but not in Japanese. The genes with altered DNA methylation were likely to be potentially useful biomarkers in the early diagnosis of NSCLC.
The nucleolar protein nucleophosmin is essential for autophagy induced by inhibiting Pol I transcription
Authors: Katagiri Naohiro , Kuroda Takao , Kishimoto Hiroyuki , Hayashi Yuki , Kumazawa Takuya , Kimura Keiji 
Published: March 2015

AbstractVarious cellular stresses activate autophagy, which is involved in lysosomal degradation of cytoplasmic materials for maintaining nutrient homeostasis and eliminating harmful components. Here, we show that RNA polymerase I (Pol I) transcription inhibition induces nucleolar disruption and autophagy. Treatment with autophagy inhibitors or siRNA specific for autophagy-related (ATG) proteins inhibited autophagy but not nucleolar disruption induced by Pol I transcription inhibition, which suggested that nucleolar disruption was upstream of autophagy. Furthermore, treatment with siRNA specific for nucleolar protein nucleophosmin (NPM) inhibited this type of autophagy. This showed that NPM was involved in autophagy when the nucleolus was disrupted by Pol I inhibition. In contrast, NPM was not required for canonical autophagy induced by nutrient starvation, as it was not accompanied by nucleolar disruption. Thus, our results revealed that, in addition to canonical autophagy, there may be NPM-dependent autophagy associated with nucleolar disruption.
Epidemiological and Etiological Characteristics of Hand, Foot and Mouth Disease in Henan, China, 2008–2013
Authors: Huang Xueyong , Wei Haiyan , Wu Shuyu , Du Yanhua , Liu Licheng , Su Jia , Xu Yuling , Wang Haifeng , Li Xingle , Wang Yanxia , Liu Guohua , Chen Weijun , Klena John David , Xu Bianli 
Published: March 2015

AbstractHand, foot and mouth disease (HFMD) is a common childhood illness caused by enteroviruses. HFMD outbreaks and reported cases have sharply increased in China since 2008. Epidemiological and clinical data of HFMD cases reported in Henan Province were collected from 2008 to 2013. Clinical specimens were obtained from a subset of these cases. Descriptive epidemiological methods were used to analyze the time, region and population distribution. The VP1 gene from EV71 and CA16 isolates was amplified and the sequences were analyzed. 400,264 cases of HFMD were reported in this study, including 22,309 severe and 141 fatal cases. Incidence peaked between April and May. Laboratory confirmation was obtained for 27,692 (6.9%) cases; EV71, CA16 and other enteroviruses accounted for 59.5%, 14.1%, 26.4%, respectively. Phylogenetic analysis revealed that EV71 belonged to the C4a evolution branch of C4 sub-genotype and CA16 belonged to subtype B1a or B1b. The occurrence of HFMD in Henan was closely related to season, age and region distribution. Children under five were the most affected population. The major pathogens causing HFMD and their genotypes have not notably changed in Henan. The data strongly support the importance of EV71 vaccination in a high population density area such as Henan, China.
Conditional-ready mouse embryonic stem cell derived macrophages enable the study of essential genes in macrophage function
Authors: Yeung A. T. Y. , Hale C. , Xia J. , Tate P. H. , Goulding D. , Keane J. A. , Mukhopadhyay S. , Forrester L. , Billker O. , Skarnes W. C. , Hancock R. E. W. , Dougan G. 
Published: March 2015

AbstractThe ability to differentiate genetically modified mouse embryonic stem (ES) cells into functional macrophages provides a potentially attractive resource to study host-pathogen interactions without the need for animal experimentation. This is particularly useful in instances where the gene of interest is essential and a knockout mouse is not available. Here we differentiated mouse ES cells into macrophages in vitro and showed, through a combination of flow cytometry, microscopic imaging and RNA-Seq, that ES cell-derived macrophages responded to S. Typhimurium, in a comparable manner to mouse bone marrow derived macrophages. We constructed a homozygous mutant mouse ES cell line in the Traf2 gene that is known to play a role in tumour necrosis factor-α signalling but has not been studied for its role in infections or response to Toll-like receptor agonists. Interestingly, traf2-deficient macrophages produced reduced levels of inflammatory cytokines in response to lipopolysaccharide (LPS) or flagellin stimulation and exhibited increased susceptibility to S. Typhimurium infection.
The Role of Receptor for Advanced Glycation End Products in Airway Inflammation in CF and CF related Diabetes
Authors: Mulrennan Siobhain , Baltic Svetlana , Aggarwal Shashi , Wood Jamie , Miranda Alina , Frost Felicity , Kaye Joey , Thompson Philip J. 
Published: March 2015

AbstractCystic Fibrosis (CF) is often accompanied by diabetes leading to worsening lung function, the reason for which is unclear. The receptor for advanced-glycation-end-products (RAGE) regulates immune responses and inflammation and has been linked to diabetes and possibly CF. We performed a pilot study to determine if CF and CF-related diabetes (CFRD) are associated with enhanced RAGE expression. Full length (fl)RAGE, soluble (s)RAGE, endogenous soluble (es)RAGE, S100A12 (enRAGE) and advanced-glycation-end-products (AGE) expression was assessed in serum, white blood cells and sputum of patients with CF; diabetes; CFRD and healthy subjects. Sputum enRAGE/sRAGE ratios were high in CF but particularly in CFRD which negatively correlated with % predicted FEV1. Serum AGE and AGE/sRAGE ratios were high in diabetics but not in CF. A complex, multifaceted approach was used to assess the role of RAGE and its ligands which is fundamental to determining their impact on airway inflammation. There is a clear association between RAGE activity in the airways of CF and CFRD patients that is not evident in the vascular compartment and correlates with lung function, in contrast to diabetes. This strongly suggests a role for RAGE in contributing to the inflammatory overdrive seen in CF and to a greater extent in CFRD.
Faraday rotation and photoluminescence in heavily Tb3+-doped GeO2-B2O3-Al2O3-Ga2O3 glasses for fiber-integrated magneto-optics
Authors: Gao Guojun , Winterstein-Beckmann Anja , Surzhenko Oleksii , Dubs Carsten , Dellith Jan , Schmidt Markus A. , Wondraczek Lothar 
Published: March 2015

AbstractWe report on the magneto-optical (MO) properties of heavily Tb3+-doped GeO2-B2O3-Al2O3-Ga2O3 glasses towards fiber-integrated paramagnetic MO devices. For a Tb3+ ion concentration of up to 9.7 × 1021 cm−3, the reported glass exhibits an absolute negative Faraday rotation of ~120 rad/T/m at 632.8 nm. The optimum spectral ratio between Verdet constant and light transmittance over the spectral window of 400–1500 nm is found for a Tb3+ concentration of ~6.5 × 1021 cm−3. For this glass, the crystallization stability, expressed as the difference between glass transition temperature and onset temperature of melt crystallization exceeds 100 K, which is a prerequisite for fiber drawing. In addition, a high activation energy of crystallization is achieved at this composition. Optical absorption occurs in the NUV and blue spectral region, accompanied by Tb3+ photoluminescence. In the heavily doped materials, a UV/blue-to-green photo-conversion gain of ~43% is achieved. The lifetime of photoluminescence is ~2.2 ms at a stimulated emission cross-section σem of ~1.1 × 10−21 cm2 for ~ 5.0 × 1021 cm−3 Tb3+. This results in an optical gain parameter σem*τ of ~2.5 × 10−24 cm2s, what could be of interest for implementation of a Tb3+ fiber laser.
Controllable magnetic correlation between two impurities by spin-orbit coupling in graphene
Authors: Hu F. M. , Kou Liangzhi , Frauenheim Thomas 
Published: March 2015

AbstractTwo magnetic impurities on the edge of a zigzag graphene nanoribbon strongly interact with each other via indirect coupling, which can be mediated by conducting carriers. By means of Quantum Monte Carlo (QMC) simulations, we find that the spin-orbit coupling λ and the chemical potential μ in system can be used to drive the transition of local-spin exchange from ferromagnetism to anti-ferromagnetism. Since the tunable ranges for λ and μ in graphene are experimentally reachable, we thus open the possibilities for its device application. The symmetry in spatial distribution is broken by the vertical and the transversal spin-spin correlations due to the effect of spin-orbit coupling, leading to the spatial anisotropy of spin exchange, which distinguish our findings from the case in normal Fermi liquid.
On/off switching of bit readout in bias-enhanced tunnel magneto-Seebeck effect
Authors: Boehnke Alexander , Milnikel Marius , von der Ehe Marvin , Franz Christian , Zbarsky Vladyslav , Czerner Michael , Rott Karsten , Thomas Andy , Heiliger Christian , Reiss Günter , Münzenberg Markus 
Published: March 2015

AbstractThermoelectric effects in magnetic tunnel junctions are promising to serve as the basis for logic devices or memories in a ”green” information technology. However, up to now the readout contrast achieved with Seebeck effects was magnitudes smaller compared to the well-established tunnel magnetoresistance effect. Here, we resolve this problem by demonstrating that the tunnel magneto-Seebeck effect (TMS) in CoFeB/MgO/CoFeB tunnel junctions can be switched on to a logic “1” state and off to “0” by simply changing the magnetic state of the CoFeB electrodes. This new functionality is achieved by combining a thermal gradient and an electric field. Our results show that the signal crosses zero and can be adjusted by tuning a bias voltage that is applied between the electrodes of the junction; hence, the name of the effect is bias-enhanced tunnel magneto-Seebeck effect (bTMS). Via the spin- and energy-dependent transmission of electrons in the junction, the bTMS effect can be configured using the bias voltage with much higher control than the tunnel magnetoresistance and even completely suppressed for only one magnetic configuration. Moreover, our measurements are a step towards the experimental realization of high TMS ratios without additional bias voltage, which are predicted for specific Co-Fe compositions.
Systematic identification and characterization of long intergenic non-coding RNAs in fetal porcine skeletal muscle development
Authors: Zhao Weimin , Mu Yulian , Ma Lei , Wang Chen , Tang Zhonglin , Yang Shulin , Zhou Rong , Hu Xiaoju , Li Meng-Hua , Li Kui 
Published: March 2015

AbstractLong intergenic non-coding RNAs (lincRNAs) play important roles in many cellular processes. Here, we present the first systematic identification and characterization of lincRNAs in fetal porcine skeletal muscle. We obtained a total of 55.02 million 90-bp paired-end reads and assembled 54,550 transcripts using cufflinks. We developed a pipeline to identify 570 multi-exon lincRNAs by integrating a set of previous approaches. These putative porcine lincRNAs share many characteristics with mammalian lincRNAs, such as a relatively short length, small number of exons and low level of sequence conservation. We found that the porcine lincRNAs were preferentially located near genes mediating transcriptional regulation rather than those with developmental functions. We further experimentally analyzed the features of a conserved mouse lincRNA gene and found that isoforms 1 and 4 of this lincRNA were enriched in the cell nucleus and were associated with polycomb repressive complex 2 (PRC2). Our results provide a catalog of fetal porcine lincRNAs for further experimental investigation of the functions of these genes in the skeletal muscle developmental process.
Maskless milling of diamond by a focused oxygen ion beam
Authors: Martin Aiden A. , Randolph Steven , Botman Aurelien , Toth Milos , Aharonovich Igor 
Published: March 2015

AbstractRecent advances in focused ion beam technology have enabled high-resolution, maskless nanofabrication using light ions. Studies with light ions to date have, however, focused on milling of materials where sub-surface ion beam damage does not inhibit device performance. Here we report on maskless milling of single crystal diamond using a focused beam of oxygen ions. Material quality is assessed by Raman and luminescence analysis and reveals that the damage layer generated by oxygen ions can be removed by non-intrusive post-processing methods such as localised electron beam induced chemical etching.
Tuning IL-2 signaling by ADP-ribosylation of CD25
Authors: Teege Sophie , Hann Alexander , Miksiewicz Maria , MacMillan Cary , Rissiek Björn , Buck Friedrich , Menzel Stephan , Nissen Marion , Bannas Peter , Haag Friedrich , Boyer Olivier , Seman Michel , Adriouch Sahil , Koch-Nolte Friedrich 
Published: March 2015

AbstractControl of immunologic tolerance and homeostasis rely on Foxp3+CD4+CD25+ regulatory T cells (Tregs) that constitutively express the high affinity receptor for Interleukin-2, CD25. Tregs proliferate in response to injections of IL-2/anti-IL-2 antibody complexes or low doses of IL-2. However, little is known about endogenous mechanisms that regulate the sensitivity of CD25 to signaling by IL-2. Here we demonstrate that CD25 is ADP-ribosylated at Arg35 in the IL-2 binding site by ecto-ADP-ribosyltransferase ARTC2.2, a toxin-related GPI-anchored ecto-enzyme. ADP-ribosylation inhibits binding of IL-2 by CD25, IL-2- induced phosphorylation of STAT5 and IL-2-dependent cell proliferation. Our study elucidates an as-yet-unrecognized mechanism to tune IL-2 signaling. This newly found mechanism might thwart Tregs at sites of inflammation and thereby permit a more potent response of activated effector T cells.
Electron-Phonon Coupling and its implication for the superconducting topological insulators
Authors: Zhang Xiao-Long , Liu Wu-Ming 
Published: March 2015

AbstractThe recent observation of superconductivity in doped topological insulators has sparked a flurry of interest due to the prospect of realizing the long-sought topological superconductors. Yet the understanding of underlying pairing mechanism in these systems is far from complete. Here we investigate this problem by providing robust first-principles calculations of the role of electron-phonon coupling for the superconducting pairing in the prime candidate CuxBi2Se3. Our results show that electron-phonon scattering process in this system is dominated by zone center and boundary optical modes, with coexistence of phonon stiffening and softening. While the calculated electron-phonon coupling constant λ suggests that Tc from electron-phonon coupling is 2 orders smaller than the ones reported on bulk inhomogeneous samples, suggesting that superconductivity may not come from pure electron-phonon coupling. We discuss the possible enhancement of superconducting transition temperature by local inhomogeneity introduced by doping.
Functional polymorphisms in the promoter region of MMP-2 and MMP-9 and susceptibility to obstructive sleep apnea
Authors: Cao Chao , Wu Bin , Wu Yanping , Yu Yiming , Ma Hongying , Sun Shifang , Zhang Qiaoli , Ding Qunli , Chen Li , Deng Zaichun 
Published: March 2015

AbstractGenetic susceptibility to obstructive sleep apnea (OSA) has been a research focus in the scientific community in the past few years. In this study, we recruited 375 subjects to investigate whether functional polymorphisms in the promoter region of matrix metalloproteinase (MMP)-2 (-1306C/T) and MMP-9 (-1562C/T) increased susceptibility to OSA. Our study showed no significant association between MMP-2 -1306C/T polymorphism and risk of OSA (T vs. C: OR = 1.01, 95% CI = 0.67–1.52; P = 0.97). Compared with the MMP-9 -1562C allele, the -1562T allele was associated with increased risk of OSA (T vs. C: OR = 1.56, 95% CI = 1.02–2.39; P = 0.04). However, neither MMP-2 -1306C/T nor MMP-9 -1562C/T polymorphism was found to be associated with severity of the disease. Our study suggested that the MMP-2 -1306C/T polymorphism was not associated with OSA susceptibility, whereas the MMP-9 -1562T allele was associated with increased risk of OSA.
Mindin regulates vascular smooth muscle cell phenotype and prevents neointima formation
Authors: Zhu Li-Hua , Huang Ling , Zhang Xiaojing , Zhang Peng , Zhang Shu-Min , Guan Hongjing , Zhang Yan , Zhu Xue-Yong , Tian Song , Deng Keqiong , Li Hongliang 
Published: March 2015

Mindin/spondin 2, an extracellular matrix (ECM) component that belongs to the thrombospondin type 1 (TSR) class of molecules, plays prominent roles in the regulation of inflammatory responses, angiogenesis and metabolic disorders. Our most recent studies indicated that mindin is largely involved in the initiation and development of cardiac and cerebrovascular diseases [Zhu et al. (2014) J. Hepatol. 60, 1046–1054; Bian et al. (2012) J. Mol. Med. 90, 895–910; Wang et al. (2013) Exp. Neurol. 247, 506–516; Yan et al. (2011) Cardiovasc. Res. 92, 85–94]. However, the regulatory functions of mindin in neointima formation remain unclear. In the present study, mindin expression was significantly down-regulated in platelet-derived growth factor-BB (PDGF-BB)-stimulated vascular smooth muscle cells (VSMCs) and wire injury-stimulated vascular tissue. Using a gain-of-function approach, overexpression of mindin in VSMCs exhibited strong anti-proliferative and anti-migratory effects on VSMCs, whereas significant suppression of intimal hyperplasia was observed in transgenic (TG) mice expressing mindin specifically in smooth muscle cells (SMCs). These mice exhibited blunted VSMC proliferation, migration and phenotypic switching. Conversely, deletion of mindin dramatically exacerbated neointima formation in a wire-injury mouse model, which was further confirmed in a balloon injury-induced vascular lesion model using a novel mindin-KO (knockout) rat strain. From a mechanistic standpoint, the AKT (Protein Kinase B)−GSK3β (glycogen synthase kinase 3β)/mTOR (mammalian target of rapamycin)−FOXO3A (forkhead box O)–FOXO1 signalling axis is responsible for the regulation of mindin during intimal thickening. Interestingly, an AKT inhibitor largely reversed mindin-KO-induced aggravated hyperplasia, suggesting that mindin-mediated neointima formation is AKT-dependent. Taken together, our findings demonstrate that mindin protects against vascular hyperplasia by suppression of abnormal VSMC proliferation, migration and phenotypic switching in an AKT-dependent manner. Up-regulation of mindin might represent an effective therapy for vascular-remodelling-related diseases.