bluuebunny/crossref_metadata_2025 huggingface dataset:
Assembly and activation of the Hippo signalome by FAT1 tumor suppressor
Authors: Martin Daniel , Degese Maria S. , Vitale-Cross Lynn , Iglesias-Bartolome Ramiro , Valera Juan Luis Callejas , Wang Zhiyong , Feng Xiaodong , Yeerna Huwate , Vadmal Vachan , Moroishi Toshiro , Thorne Rick F. , Zaida Moraima , Siegele Bradford , Cheong Sok C. , Molinolo Alfredo A. , Samuels Yardena , Tamayo Pablo , Guan Kun Liang , Lippman Scott M. , Lyons J. Guy , Gutkind J. Silvio
Published: June 2018

Dysregulation of the Hippo signaling pathway and the consequent YAP1 activation is a frequent event in human malignancies, yet the underlying molecular mechanisms are still poorly understood. A pancancer analysis of core Hippo kinases and their candidate regulating molecules revealed few alterations in the canonical Hippo pathway, but very frequent genetic alterations in the FAT family of atypical cadherins. By focusing on head and neck squamous cell carcinoma (HNSCC), which displays frequent FAT1 alterations (29.8%), we provide evidence that FAT1 functional loss results in YAP1 activation. Mechanistically, we found that FAT1 assembles a multimeric Hippo signaling complex (signalome), resulting in activation of core Hippo kinases by TAOKs and consequent YAP1 inactivation. We also show that unrestrained YAP1 acts as an oncogenic driver in HNSCC, and that targeting YAP1 may represent an attractive precision therapeutic option for cancers harboring genomic alterations in the FAT1 tumor suppressor genes.
The Wave2 scaffold Hem-1 is required for transition of fetal liver hematopoiesis to bone marrow
Authors: Shao Lijian , Chang Jianhui , Feng Wei , Wang Xiaoyan , Williamson Elizabeth A. , Li Ying , Schajnovitz Amir , Scadden David , Mortensen Luke J. , Lin Charles P. , Li Linheng , Paulson Ariel , Downing James , Zhou Daohong , Hromas Robert A.
Published: June 2018

The transition of hematopoiesis from the fetal liver (FL) to the bone marrow (BM) is incompletely characterized. We demonstrate that the Wiskott–Aldrich syndrome verprolin-homologous protein (WAVE) complex 2 is required for this transition, as complex degradation via deletion of its scaffold Hem-1 causes the premature exhaustion of neonatal BM hematopoietic stem cells (HSCs). This exhaustion of BM HSC is due to the failure of BM engraftment of Hem-1−/− FL HSCs, causing early death. The Hem-1−/− FL HSC engraftment defect is not due to the lack of the canonical function of the WAVE2 complex, the regulation of actin polymerization, because FL HSCs from Hem-1−/− mice exhibit no defects in chemotaxis, BM homing, or adhesion. Rather, the failure of Hem-1−/− FL HSC engraftment in the marrow is due to the loss of c-Abl survival signaling from degradation of the WAVE2 complex. However, c-Abl activity is dispensable for the engraftment of adult BM HSCs into the BM. These findings reveal a novel function of the WAVE2 complex and define a mechanism for FL HSC fitness in the embryonic BM niche.
Publisher Correction: A multistage rotational speed changing molecular rotor regulated by pH and metal cations
Authors: Wu Yingying , Wang Guangxia , Li Qiaolian , Xiang Junfeng , Jiang Hua , Wang Ying
Published: June 2018

The original version of this Article omitted the Received and Accepted dates; they should have been 22nd January 2018 and 19th April 2018, respectively. This has been corrected in the PDF and HTML versions of the Article.
Molecular signature of progenitor cells isolated from young and adult human hearts
Authors: Walravens Ann-Sophie , Vanhaverbeke Maarten , Ottaviani Lara , Gillijns Hilde , Trenson Sander , Driessche Nina Vanden , Luttun Aernout , Meyns Bart , Herijgers Paul , Rega Filip , Heying Ruth , Sampaolesi Maurilio , Janssens Stefan
Published: June 2018

The loss of endogenous cardiac regenerative capacity within the first week of postnatal life has intensified clinical trials to induce cardiac regeneration in the adult mammalian heart using different progenitor cell types. We hypothesized that donor age-related phenotypic and functional characteristics of cardiac progenitor cells (CPC) account for mixed results of cell-based cardiac repair. We compared expression profiles and cell turnover rates of human heart-derived c-kitpos progenitors (c-kitpos CPC) and cardiosphere-derived cells (CDC) from young and adult donor origin and studied their in vitro angiogenic and cardiac differentiation potential, which can be relevant for cardiac repair. We report that 3-dimensional CDC expansion recapitulates a conducive environment for growth factor and cytokine release from adult donor cells (aCDC) that optimally supports vascular tube formation and vessel sprouting. Transdifferentiation capacity of c-kitpos CPCs and CDCs towards cardiomyocyte-like cells was modest, however, most notable in young c-kitpos cells and adult CDCs. Progenitors isolated with different methods thus show cell- and donor-specific characteristics that may account for variable contributions in functional myocardial recovery.
Intraflagellar transport 46 (IFT46) is essential for trafficking IFT proteins between cilia and cytoplasm in Paramecium
Authors: Shi Lei , Shi Xuezhen , Shen Yuan
Published: June 2018

Intraflagellar transport (IFT) is a bi-directional process by which particles are carried within the cilia or flagella. This process is essential for ciliary growth and functional maintenance. The IFT complex B (IFTB) is linked to a kinesin motor for anterograde transport towards the ciliary tip. The IFT complex A (IFTA) is connected to a dynein motor for retrograde transport towards the ciliary basis. This study focuses on IFT46, an IFTB member that participates in this process. InParamecium, a GFP-labelled IFT46 protein was found in basal bodies and in some cilia, mostly those undergoing biogenesis. RNA interference against IFT46 inParameciumtriggered severe defects in ciliary growth and architecture, including a decreased cilia number and shortened cilia length. This result differed from that obtained from the cells that were depleted of IFT80, another IFTB protein. Moreover, IFT57-GFP fusion protein abnormally accumulated in the cortex and cytoplasm in IFT46-depleted cells compared with the control. Furthermore, transcriptomic analysis showed that IFT46 depletion induced the abnormal expression of several genes that encodeding kinesin and dynein chains. These findings together indicate that IFT46 plays important roles in trafficking IFT proteins between the cytoplasm and cilia ofParamecium.
Preimplantation Genetic Screening with Spent Culture Medium/Blastocoel Fluid for in Vitro Fertilization
Authors: Li Penghao , Song Zhe , Yao Yaxin , Huang Tianhua , Mao Rurong , Huang Jun , Ma Yongyi , Dong Xin , Huang Wenlong , Huang Jihua , Chen Tianjian , Qu Ting , Li Lingxiao , Zhong Ying , Gu Jiang
Published: June 2018

Preimplantation genetic screening (PGS) detects chromosomal aneuploidy from DNA extracted from trophectodermal biopsy of the embryos before implantation. Although a controlled study showed no difference in pregnancy rates between this invasive cell biopsy technique and a non-biopsied control group, the potential long-term damage by the current PGS method has not be completely ruled out. We therefore tested a less-invasive protocol which utilizes spent culture medium combining with blastocoel fluid (ECB) to assess chromosomal aneuploidy. We compared the new protocol with the currently employed trophectodermal biopsy method against chromosomal information obtained from the remaining embryo. We found that the new technique generated information about aneuploidy that was not entirely identical to obtained from the biopsied trophectoderm or the remaining embryo. As the origins of the DNA extracted from the three sample types were not the same, the significance and interpretation of each result would have its own meaning. The possible implications derived from the ECB results as well as those from cell biopsy were discussed. The effectiveness of this new approach in selecting the best embryo for uterine implantation awaits further long term evaluation.
Dynamic evolution and phylogenomic analysis of the chloroplast genome in Schisandraceae
Authors: Li Bin , Zheng Yongqi
Published: June 2018

Chloroplast genomes of plants are highly conserved in both gene order and gene content, are maternally inherited, and have a lower rate of evolution. Chloroplast genomes are considered to be good models for testing lineage-specific molecular evolution. In this study, we use Schisandraceae as an example to generate insights into the overall evolutionary dynamics in chloroplast genomes and to establish the phylogenetic relationship of Schisandraceae based on chloroplast genome data using phylogenomic analysis. By comparing three Schisandraceae chloroplast genomes, we demonstrate that the gene order, gene content, and length of chloroplast genomes in Schisandraceae are highly conserved but experience dynamic evolution among species. The number of repeat variations were detected, and the Schisandraceae chloroplast genome was revealed as unusual in having a 10 kb contraction of the IR due to the genome size variations compared with other angiosperms. Phylogenomic analysis based on 82 protein-coding genes from 66 plant taxa clearly elucidated that Schisandraceae is a sister to a clade that includes magnoliids, monocots, and eudicots within angiosperms. As to genus relationships within Schisandraceae, Kadsura and Schisandra formed a monophyletic clade which was sister to Illicium.
Influence of oxygen on generation of reactive chemicals from nitrogen plasma jet
Authors: Uhm Han Sup , Ki Se Hoon , Baik Ku Youn , Choi Eun Ha
Published: June 2018

A nonthermal plasma jet is operated at atmospheric pressure inside a vacuum chamber filled with nitrogen gas. Various chemical compounds are fabricated from nitrogen and water molecules in plasma jet with varying oxygen content. Detailed theoretical investigation of these chemical compounds is carried out in terms of different oxygen ratio ξ. Experimental measurements are also carried out for comparison with theoretical results. Hydroxyl molecules are mostly generated at surface of water, and some of them can penetrate into water. The density of hydroxyl molecules has its maximum without oxygen, and decreases to zero as ξ increases to 0.25. The density of the ammonia of NH3 also deceases as ξ increases to 0.25. On the other hand, theory and experiment show that the density of the NO3 increases drastically as ξ increases to 0.25. The hydrogen peroxide density in plasma activated water deceases, reaches its minimum value at ξ = 0.05, and then increases again, as ξ increases from a small value to a large value. The pH value of the plasma activated water, which is slightly changed to alkali without oxygen, decreases as ξ increases.
Numerical emulation of Thru-Reflection-Line calibration for the de-embedding of Surface Acoustic Wave devices
Authors: Mencarelli D. , Djafari-Rouhani B. , Pennec Y. , Pitanti A. , Zanotto S. , Stocchi M. , Pierantoni L.
Published: June 2018

In this contribution, a rigorous numerical calibration is proposed to characterize the excitation of propagating mechanical waves by interdigitated transducers (IDTs). The transition from IDT terminals to phonon waveguides is modeled by means of a general circuit representation that makes use of Scattering Matrix (SM) formalism. In particular, the three-step calibration approach called the Thru-Reflection-Line (TRL), that is a well-established technique in microwave engineering, has been successfully applied to emulate typical experimental conditions. The proposed procedure is suitable for the synthesis/optimization of surface-acoustic-wave (SAW) based devices: the TRL calibration allows to extract/de-embed the acoustic component, namely resonator or filter, from the outer IDT structure, regardless of complexity and size of the letter. We report, as a result, the hybrid scattering parameters of the IDT transition to a mechanical waveguide formed by a phononic crystal patterned on a piezoelectric AlN membrane, where the effect of a discontinuity from periodic to uniform mechanical waveguide is also characterized. In addition, to ensure the correctness of our numerical calculations, the proposed method has been validated by independent calculations.
Direct current stimulation of endothelial monolayers induces a transient and reversible increase in transport due to the electroosmotic effect
Authors: Cancel Limary M. , Arias Katherin , Bikson Marom , Tarbell John M.
Published: June 2018

We investigated the effects of direct current stimulation (DCS) on fluid and solute transport across endothelial cell (EC) monolayersin vitro. Our motivation was transcranial direct current stimulation (tDCS) that has been investigated for treatment of neuropsychiatric disorders, to enhance neurorehabilitation, and to change cognition in healthy subjects. The mechanisms underlying this diversity of applications remain under investigation. To address the possible role of blood-brain barrier (BBB) changes during tDCS, we applied direct current to cultured EC monolayers in a specially designed chamber that generated spatially uniform direct current. DCS induced fluid and solute movement across EC layers that persisted only for the duration of the stimulation suggesting an electroosmosis mechanism. The direction of induced transport reversed with DCS polarity – a hallmark of the electroosmotic effect. The magnitude of DCS-induced flow was linearly correlated to the magnitude of the applied current. A mathematical model based on a two-pore description of the endothelial transport barrier and a Helmholtz model of the electrical double layer describes the experimental data accurately and predicts enhanced significance of this mechanism in less permeable monolayers. This study demonstrates that DCS transiently alters the transport function of the BBB suggesting a new adjunct mechanism of tDCS.
Uncovering global metabolic response to cordycepin production in Cordyceps militaris through transcriptome and genome-scale network-driven analysis
Authors: Raethong Nachon , Laoteng Kobkul , Vongsangnak Wanwipa
Published: June 2018

The cellular metabolic adaptations ofCordyceps militarishave been progressively studied. In particular, the cordycepin pathway is of interest in medicinal applications. Even though the metabolic pathways for cordycepin production are known to be related to different carbon sources, the regulatory mechanisms at a systems level are poorly characterized. To explore the regulatory mechanisms, this study therefore aimed to investigate the global metabolic response to cordycepin production inC. militaristhrough transcriptome analysis and genome-scale network-driven analysis. Here, transcriptome analysis of 16,805 expressed genes inC. militarisstrain TBRC6039 grown on different carbon sources was performed. Of these genes, 2,883 were significantly differentially expressed genes, uncovering sucrose- and glucose-mediated changes in the transcriptional regulation of central carbon metabolism inC. militaris, which was shown using the CmSNF1 mechanism as an example. After applying genome-scale metabolic network-driven analysis, reporter metabolites and key metabolic subnetworks involving adenosine, cordycepin and methionine were proposed through the up-regulation of cordycepin biosynthetic genes. Our findings suggest that the transcriptional regulation of these pathways is a ubiquitous feature in response to specific culture conditions during cordycepin overproduction.
Low circulating chemerin levels correlate with hepatic dysfunction and increased mortality in decompensated liver cirrhosis
Authors: Horn Paul , von Loeffelholz Christian , Forkert Franziska , Stengel Sven , Reuken Philipp , Aschenbach René , Stallmach Andreas , Bruns Tony
Published: June 2018

Nutritional status, infections, inflammation and extrahepatic organ dysfunction are critical factors for the progression of chronic liver disease. Chemerin is an immune-metabolically and chemotactically active adipokine and we hypothesized that it is associated with disease severity and prognosis in patients with advanced decompensated cirrhosis. Therefore, we measured serum concentrations of chemerin in a prospectively characterized cohort of 80 patients with decompensated cirrhosis and ascites and assessed the associations with markers of disease severity and short-term outcome at 28 days. In a subset of patients (n = 40), ascitic fluid chemerin was determined. Advanced liver disease was associated with decreased serum but not ascitic chemerin levels. Serum chemerin correlated with markers of hepatic function (total bilirubin, albumin, INR) and inversely correlated with indicators of portal hypertension (platelet count, gastrointestinal bleeding) but not with extrahepatic organ failure and systemic inflammation. Patients presenting with acute-on-chronic liver failure or infection did not exhibit altered serum or ascitic fluid chemerin concentrations. However, serum chemerin levels below 87 ng/ml predicted an increased risk for mortality or liver transplantation within 28 days independently of MELD and infections. We conclude that low serum chemerin is an independent adverse prognostic factor in patients with advanced decompensated cirrhosis.
Inhibition of Semicarbazide-sensitive Amine Oxidase Reduces Atherosclerosis in Cholesterol-fed New Zealand White Rabbits
Authors: Wang Shu-Huei , Yu Tse-Ya , Hung Chi-Sheng , Yang Chung-Yi , Lin Mao-Shin , Su Chien-Yin , Chen Yuh-Lien , Kao Hsien-Li , Chuang Lee-Ming , Tsai Feng-Chiao , Li Hung-Yuan
Published: June 2018

Inflammation, oxidative stress, and the formation of advanced glycated end-products (AGEs) are important components of atherosclerosis. Vascular adhesion protein-1 (VAP-1) participates in inflammation. Its enzymatic activity, semicarbazide-sensitive amine oxidase (SSAO), can catalyze oxidative deamination reactions to produce hydrogen peroxide and aldehydes, leading to the subsequent generation of AGEs. This study aimed to investigate the effect of VAP-1/SSAO inhibition on atherosclerosis. In our study, immunohistochemical staining showed that atherosclerotic plaques displayed higher VAP-1 expression than normal arterial walls in apolipoprotein E-deficient mice, cholesterol-fed New Zealand White rabbits and humans. In cholesterol-fed rabbits, VAP-1 was expressed on endothelial cells and smooth muscle cells in the thickened intima of the aorta. Treatment with PXS-4728A, a selective VAP-1/SSAO inhibitor, in cholesterol-fed rabbits significantly decreased SSAO-specific hydrogen peroxide generation in the aorta and reduced atherosclerotic plaques. VAP-1/SSAO inhibition also lowered blood low-density lipoprotein cholesterol, reduced the expression of adhesion molecules and inflammatory cytokines, suppressed recruitment and activation of macrophages, and decreased migration and proliferation of SMC. In conclusion, VAP-1/SSAO inhibition reduces atherosclerosis and may act through suppression of several important mechanisms for atherosclerosis.
Dispersion mapping as a simple postprocessing step for Fourier domain Optical Coherence Tomography data
Authors: Kolenderska Sylwia M. , Bräuer Bastian , Vanholsbeeck Frédérique
Published: June 2018

Optical Coherence Tomography (OCT) was originally conceived as a volumetric imaging method. Quickly, OCT images went beyond structural data and started to provide functional information about an object enabling for example visualization of blood flow or tissue elasticity. Minimal or no need for system alterations make functional OCT techniques useful in performing multimodal imaging, where differently contrasted images are produced in a single examination. We propose a method that further extends the current capabilities of OCT and requires no modifications to the system. Our algorithm provides information about the sample’s Group Velocity Dispersion (GVD) and can be easily applied to any OCT dataset acquired with a Fourier domain system. GVD is calculated from the difference in material’s optical thickness measured from two images obtained for different spectral ranges. Instead of using two separate light sources, we propose to apply a filter-based, numerical procedure that synthesizes two spectra from one broadband spectrum. We discuss the limitations of the method and present GVD values for BK7 and sapphire and ocular media: cornea and aqueous humour of a rat eye. Results corroborate previous measurements using two different light sources.
Computational screening of organic polymer dielectrics for novel accelerator technologies
Authors: Pilania Ghanshyam , Weis Eric , Walker Ethan M. , Gilbertson Robert D. , Muenchausen Ross E. , Simakov Evgenya I.
Published: June 2018

The use of infrared lasers to power accelerating dielectric structures is a developing area of research. Within this technology, the choice of the dielectric material forming the accelerating structures, such as the photonic band gap (PBG) structures, is dictated by a range of interrelated factors including their dielectric and optical properties, amenability to photo-polymerization, thermochemical stability and other target performance metrics of the particle accelerator. In this direction, electronic structure theory aided computational screening and design of dielectric materials can play a key role in identifying potential candidate materials with the targeted functionalities to guide experimental synthetic efforts. In an attempt to systematically understand the role of chemistry in controlling the electronic structure and dielectric properties of organic polymeric materials, here we employ empirical screening and density functional theory (DFT) computations, as a part of our multi-step hierarchal screening strategy. Our DFT based analysis focused on the bandgap, dielectric permittivity, and frequency-dependent dielectric losses due to lattice absorption as key properties to down-select promising polymer motifs. In addition to the specific application of dielectric laser acceleration, the general methodology presented here is deemed to be valuable in the design of new insulators with an attractive combination of dielectric properties.
BMP and WNT signalling cooperate through LEF1 in the neuronal specification of adult hippocampal neural stem and progenitor cells
Authors: Armenteros Tomás , Andreu Zoraida , Hortigüela Rafael , Lie D. Chichung , Mira Helena
Published: June 2018

Neuronal production from neural stem cells persists during adulthood in the subgranular zone of the hippocampal dentate gyrus. Extracellular signals provided by the hippocampal microenvironment regulate the neuronal fate commitment of the stem cell progeny. To date, the identity of those signals and their crosstalk has been only partially resolved. Here we show that adult rat hippocampal neural stem and progenitor cells (AH-NSPCs) express receptors for bone morphogenetic proteins (BMPs) and that the BMP/P-Smad pathway is active in AH-NSPCs undergoing differentiation towards the neuronal lineage. In vitro, exposure to the BMP2 and BMP4 ligands is sufficient to increase neurogenesis from AH-NSPCs in a WNT dependent manner while decreasing oligodendrogenesis. Moreover, BMP2/4 and WNT3A, a key regulator of adult hippocampal neurogenesis, cooperate to further enhance neuronal production. Our data point to a mechanistic convergence of the BMP and WNT pathways at the level of the T-cell factor/lymphoid enhancer factor gene Lef1. Altogether, we provide evidence that BMP signalling is an important regulator for the neuronal fate specification of AH-NSPCs cultures and we show that it significantly cooperates with the previously described master regulator of adult hippocampal neurogenesis, the WNT signalling pathway.
Comparative assessment of Graves’ disease and main extrathyroidal manifestation, Graves’ ophthalmopathy, by non-targeted metabolite profiling of blood and orbital tissue
Authors: Ji Dong Yoon , Park Se Hee , Park Soo Jin , Kim Kyoung Heon , Ku Cheol Ryong , Shin Dong Yeob , Yoon Jin Sook , Lee Do Yup , Lee Eun Jig
Published: June 2018

Graves’ disease (GD) is an autoimmune disorder that causes the overproduction of thyroid hormones and consequent cascade of systemic metabolism dysfunction. Moreover, Graves’ ophthalmopathy (GO) is the main extrathyroidal manifestation of Graves’ disease (GD). The goal of the study was to identify metabolic signatures in association with diagnostic biomarkers of GD without GO and GO, respectively. Ninety metabolites were profiled and analyzed based on a non-targeted primary metabolite profiling from plasma samples of 21 GD patients without GO, 26 subjects with GO, and 32 healthy subjects. Multivariate statistics showed a clear discrimination between healthy controls and disease group (R2Y = 0.518, Q2 = 0.478) and suggested a biomarker panel consisting of 10 metabolites. Among them, most of metabolites showed the positive association with the levels of thyrotropin receptor antibodies. With combination of proline and 1,5-anhydroglucitol, which were identified as GO-specific modulators, the re-constructed biomarker model greatly improved the statistical power and also facilitated simultaneous discrimination among healthy control, GO, and GD without GO groups (AUC = 0.845–0.935). Finally, the comparative analysis of tissue metabolite profiles from GO patients proposed putative metabolic linkage between orbital adipose/connective tissues and the biofluidic consequences, in which fumarate, proline, phenylalanine, and glycerol were coordinately altered with the blood metabolites.
Mycobacterium terramassiliense, Mycobacterium rhizamassiliense and Mycobacterium numidiamassiliense sp. nov., three new Mycobacterium simiae complex species cultured from plant roots
Authors: Bouam A. , Armstrong N. , Levasseur A. , Drancourt M.
Published: June 2018

Three slowly growing mycobacteria named strain AB308, strain AB215 and strain AB57 were isolated from the tomato plant roots. The 16S rRNA and rpoB gene sequence analyses suggested that each strain was representative of one hitherto unidentified slowly-growing Mycobacterium species of the Mycobacterium simiae complex. Genome sequencing indicated that each strain contained one chromosome of 6.015–6.029 Mbp. A total of 1,197, 1,239 and 1,175 proteins were found to be associated with virulence and 107, 76 and 82 proteins were associated with toxin/antitoxin systems for strains AB308, AB215 and AB57, respectively. The three genomes encode for secondary metabolites, with 38, 33 and 46 genes found to be associated with polyketide synthases/non-ribosomal peptide synthases and nine, seven and ten genes encoding for bacteriocins, respectively. The genome of strain AB308 encodes for one questionable prophage and three incomplete prophages, while only incomplete prophages were predicted in AB215 and AB57 genomes. Genetic and genomic data indicate that strains AB308, AB215 and AB57 are each representative of a new Mycobacterium species that we respectively named Mycobacterium terramassiliense, Mycobacterium numidiamassiliense and Mycobacterium rhizamassiliense.
Selection and Validation of Reference Genes for mRNA Expression by Quantitative Real-Time PCR Analysis in Neolamarckia cadamba
Authors: Huang Tian , Long Jianmei , Liu Si-Wen , Yang Zi-Wei , Zhu Qi-Jin , Zhao Xiao-Lan , Peng Changcao
Published: June 2018

Neolamarckia cadamba is an economically-important fast-growing tree species in South China and Southeast Asia. As a prerequisite first step for future gene expression studies, we have identified and characterized a series of stable reference genes that can be used as controls for quantitative real time PCR (qRT-PCR) expression analysis in this study. The expression stability of 15 candidate reference genes in various tissues and mature leaves under different conditions was evaluated using four different algorithms, i.e., geNorm, NormFinder, BestKeeper and RefFinder. Our results showed that SAMDC was the most stable of the selected reference genes across the set of all samples, mature leaves at different photosynthetic cycles and under drought stress, whereas RPL10A had the most stable expression in various tissues. PGK and RPS25 were considered the most suitable reference for mature leaves at different developmental stages and under cold treatment, respectively. Additionally, the gene expression profiles of sucrose transporter 4 (NcSUT4), and 9‐cis‐epoxycarotenoid dioxygenase 3 (NcNCED3) were used to confirm the validity of candidate reference genes. Collectively, our study is the first report to validate the optimal reference genes for normalization under various conditions in N. cadamba and will benefit the future discovery of gene function in this species.
Inhibitory effects of isocryptotanshinone on gastric cancer
Authors: Chen Zhang-Ming , Huang Lei , Li Miao-Miao , Meng Lei , Ying Song-Cheng , Xu A-Man
Published: June 2018

Gastric cancer (GC) is one of the most common digestive malignancies globally, and the prognosis of patients with advanced tumors remains poor. Isocryptotanshinone (ICTS), isolated from Salvia miltiorrhiza, was found to inhibit the proliferation of lung and breast cancer cells. However, whether ICTS has anticancer activities against GC is unknown. In the present study, we reported that the proliferation of GC cells was inhibited by ICTS in a dose- and time-dependent manner. After treatment with ICTS, GC cells were arrested in the G1/G0 phase of cell cycle and the apoptotic cells were induced in a dose-dependent manner. Additionally, ICTS suppressed the expression of cell cycle- and apoptosis-associated proteins (e.g., Cyclin D1, phosphorylated Rb, E2F1, Mcl-1, Bcl-2, and Survivin). ICTS inhibited the phosphorylation of STAT3 in a dose-dependent manner. Down-regulated STAT3 attenuated the expression of Cyclin D1, p-Rb, and Survivin, which remarkably increased the sensitivity of ICTS in GC cells; overexpression of STAT3 restored the cell growth and proliferation and the protein expression suppressed by ICTS. ICTS also suppressed the xenograft tumor growth in BALB/c nude mice. Together, these data indicate that ICTS inhibits GC proliferation by inducing G1/G0 cell cycle arrest and apoptosis via inhibiting the STAT3 signaling pathway.
Prognostic value of culprit artery double-stranded DNA in ST-segment elevated myocardial infarction
Authors: Wang Xiqiang , Yang Dandan , Liu Jing , Fan Xiude , Ma Aiqun , Liu Ping
Published: June 2018

The double-stranded DNA (dsDNA) which is scaffold of neutrophil extracellular traps (NETs) has been reported to be associated with the occurrence of major adverse cardiovascular events (MACEs) in patients with coronary atherosclerosis. However, the relationship between the dsDNA and the occurrence of MACEs in patients with ST-segment elevated myocardial infarction (STEMI) remains unclear. In this study, 142 consecutive STEMI patients were admitted to medical institutions. Blood from the infarct-related coronary artery (ICA) and peripheral artery (PA) were obtained during percutaneous coronary intervention. Clinical follow-up was performed to analyze the occurrence of MACEs. Patients were divided into low ds-DNA group and high dsDNA group according to the cut-off value of ICA dsDNA. Mean follow-up time was 24.52 months in low dsDNA group and 25.71 months in high dsDNA group. dsDNA in the ICA was significantly higher than in the PA (p = 0.038) and Spearman's correlation analysis showed that they were positively correlated (r = 0.758; p < 0.01). ICA dsDNA correlated negatively with ST-segment resolution (r = −0.227; p = 0.007). The long-term MACEs rate was higher in high dsDNA group than low dsDNA group (23.7 vs. 6.7%, p = 0.015). The ICA dsDNA (OR 7.43 95% CI 1.25 to 4.07, p = 0.027), Killip class (OR 5.01 95% CI 1.11 to 4.37, p = 0.025), BMI (OR 1.36 95% CI 1.06 to 1.7, p = 0.016) and white blood cell count (OR 1.27 95% CI 1.03 to 1.57, p = 0.024) were independent predictors of the occurrence of MACEs.
Integrated microRNA and mRNA expression profiling reveals a complex network regulating pomegranate (Punica granatum L.) seed hardness
Authors: Luo Xiang , Cao Da , Zhang Jianfeng , Chen Li , Xia Xiaocong , Li Haoxian , Zhao Diguang , Zhang Fuhong , Xue Hui , Chen Lina , Li Yongzhou , Cao Shangyin
Published: June 2018

The breeding of new soft-seeded pomegranate cultivars provides new products for the market and increases farmers’ incomes, yet the genetic architecture mediating seed hardness is largely unknown. Here, the seed hardness and hundred-seed weights of 26 cultivars were determined in 2 successive years. We conducted miRNA and mRNA sequencing to analyse the seeds of two varieties of Punica granatum: soft-seeded Tunisia and hard-seeded Sanbai, at 60 and 120 d after flowering. Seed hardness was strongly positively correlated with hundred-seed weight. We detected 25 and 12 differentially expressed miRNA–mRNA pairs with negative regulatory relationships between the two genotypes at 60 and 120 d after flowering, respectively. These miRNA–mRNA pairs mainly regulated seed hardness by altering cell wall structure. Transcription factors including NAC1, WRKY and MYC, which are involved in seed hardness, were targeted by differentially expressed mdm-miR164e and mdm-miR172b. Thus, seed hardness is the result of a complex biological process regulated by a miRNA–mRNA network in pomegranate. These results will help us understand the complexity of seed hardness and help to elucidate the miRNA-mediated molecular mechanisms that contribute to seed hardness in pomegranate.
Effect of tyrosine kinase inhibitors on renal handling of creatinine by MATE1
Authors: Omote Saki , Matsuoka Natsumi , Arakawa Hiroshi , Nakanishi Takeo , Tamai Ikumi
Published: June 2018

Creatinine is actively secreted across tubular epithelial cells via organic cation transporter 2 (OCT2) and multidrug and toxin extrusion 1 (MATE1). We previously showed that the tyrosine kinase inhibitor (TKI) crizotinib inhibits OCT2-mediated transport of creatinine. In the present work, we examined the inhibitory potency of TKIs, including crizotinib, on MATE1-mediated transport of creatinine. Then, we used the kinetic parameters estimated in this and the previous work to predict the potential impact of TKIs on serum creatinine level (SCr) via reversible inhibition of creatinine transport. Crizotinib inhibited [14C]creatinine uptake by MATE1-overexpressing cells, and the inhibitory effect increased with incubation time, being greater in the case of pre-incubation or combined pre-incubation/co-incubation (pre/co-incubation) than in the case of co-incubation alone. The inhibition was non-competitive, with K
i
values of 2.34 μM, 0.455 μM and 0.342 μM under co-, pre- or pre/co-incubation conditions, respectively. Similar values were obtained for inhibition of [3H]MPP+ uptake by MATE1-overexpressing cells. Gefitinib, imatinib, pazopanib, sorafenib, and sunitinib also inhibited MATE1-mediated creatinine uptake. Further, all these TKIs except pazopanib inhibited [14C]creatinine uptake by OCT2-overexpressing cells. In rat kidney slices, the ratio of unbound tissue accumulation of TKIs to extracellular concentration ranged from 2.05 to 3.93. Prediction of the influence of TKIs on SCr based on the renal creatinine clearance and plasma maximum unbound concentrations of TKIs suggested that crizotinib and imatinib might increase SCr by more than 10% in the clinical context. Accordingly, it is necessary to be cautious in diagnosing TKI-induced renal failure only on the basis of an increase of SCr.
Impact of bronchiectasis on outcomes of hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease: A propensity matched analysis
Authors: Crisafulli Ernesto , Guerrero Mónica , Ielpo Antonella , Ceccato Adrian , Huerta Arturo , Gabarrús Albert , Soler Néstor , Chetta Alfredo , Torres Antoni
Published: June 2018

The coexistence of both Chronic Obstructive Pulmonary Disease (COPD) and bronchiectasis (BE) define an emerging phenotype with a worse prognosis; however, data about these patients do not consider baseline characteristics as confounders. We evaluate the impact of BE on outcomes of hospitalized patients with acute exacerbation of COPD (AECOPD). We prospectively considered AECOPD patients, analysed using a propensity score matching (PSM) method. The outcomes included length of hospital stay, use of non-invasive and invasive mechanical ventilation, intensive care unit admission, and mortality up to 3-years. Out of the 449 patients enrolled, 160 had associated BE. AECOPD with BE were older, had lower body mass index and greater functional impairment and severity of symptoms than AECOPD without BE. After PSM, 91 patients were considered for each group and no significant differences were found for all baseline characteristics. In full cohort, the cumulative mortality rate, the survival time, the Kaplan-Meier survival curves and the risk of death were worse in AECOPD with BE in the follow-up of 6-months, 1-year and 3-years. After PSM, data on mortality were similar between AECOPD with and without BE. In conclusion, in AECOPD patients the presence of BE does not influence mortality in a long-term follow-up.
Electrical properties, substrate specificity and optogenetic potential of the engineered light-driven sodium pump eKR2
Authors: Grimm Christiane , Silapetere Arita , Vogt Arend , Bernal Sierra Yinth Andrea , Hegemann Peter
Published: June 2018

A new microbial rhodopsin class that actively transports sodium out of the cell upon illumination was described in 2013. However, poor membrane targeting of the first-identified sodium pump KR2 in mammalian cells has hindered the direct electrical investigation of its transport mechanism and optogenetic application to date. Accordingly, we designed enhanced KR2 (eKR2), which exhibits improved membrane targeting and higher photocurrents in mammalian cells to facilitate molecular characterization and future optogenetic applications. Our selectivity measurements revealed that stationary photocurrents are primarily carried by sodium, whereas protons only play a minor role, if any. Combining laser-induced photocurrent and absorption measurements, we found that spectral changes were not necessarily related to changes in transport activity. Finally, we showed that eKR2 can be expressed in cultured hippocampal mouse neurons and induce reversible inhibition of action potential firing with millisecond precision upon illumination with moderate green-light. Hence, the light-driven sodium pump eKR2 is a reliable inhibitory optogenetic tool applicable to situations in which the proton and chloride gradients should not be altered.
Fast and robust population transfer with a Josephson qutrit via shortcut to adiabaticity
Authors: Feng Zhi-Bo , Lu Xiao-Jing , Yan Run-Ying , Zhao Zheng-Yin
Published: June 2018

We propose an effective scheme to implement fast and robust population transfer with a Josephson qutrit via shortcut to adiabaticity. Facilitated by the level-transition rule, a Λ-configuration resonant interaction can be realized between microwave drivings and the qutrit with sufficient level anharmonicity, from which we perform the reversible population transfers via invariant-based shortcut. Compared with the detuned drivings, the utilized resonant drivings shorten the transfer times significantly. Further analysis of the dependence of transfer time on Rabi couplings is helpful to experimental investigations. Thanks to the accelerated process, transfer operation is highly insensitive to noise effects. Thus the protocol could provide a promising avenue to experimentally perform fast and robust quantum operations on Josephson artificial atoms.
Global analysis of threonine metabolism genes unravel key players in rice to improve the abiotic stress tolerance
Authors: Muthuramalingam Pandiyan , Krishnan Subramanian Radhesh , Pandian Subramani , Mareeswaran Narayanan , Aruni Wilson , Pandian Shunmugiah Karutha , Ramesh Manikandan
Published: June 2018

The diversity in plant metabolites with improved phytonutrients is essential to achieve global food security and sustainable crop yield. Our study using computational metabolomics genome wide association study (cmGWAS) reports on a comprehensive profiling of threonine (Thr) metabolite in rice. Sixteen abiotic stress responsive (AbSR) – Thr metabolite producing genes (ThrMPG), modulate metabolite levels and play a significant role determining both physiological and nutritional importance of rice. These AbSR-ThrMPG were computationally analysed for their protein properties using OryzaCyc through plant metabolic network analyser. A total of 1373 and 1028 SNPs were involved in complex traits and genomic variations. Comparative mapping of AbSR-ThrMPG revealed the chromosomal colinearity with C4 grass species. Further, computational expression pattern of these genes predicted a differential expression profiling in diverse developmental tissues. Protein interaction of protein coding gene sequences revealed that the abiotic stresses (AbS) are multigenic in nature.In silicoexpression of AbSR-ThrMPG determined the putative involvement in response to individual AbS. This is the first comprehensive genome wide study reporting on AbSR –ThrMPG analysis in rice. The results of this study provide a pivotal resource for further functional investigation of these key genes in the vital areas of manipulating AbS signaling in rice improvement.
Overcoming the quantum efficiency-lifetime tradeoff of photocathodes by coating with atomically thin two-dimensional nanomaterials
Authors: Wang Gaoxue , Yang Ping , Moody Nathan A. , Batista Enrique R.
Published: June 2018

Photocathodes are key components of electron injectors for X-ray free electron laser and X-ray energy recovery linacs, which generate brilliant, ultrafast, and coherent X-rays for the exploration of matter with ultrahigh resolutions in both space and time. Whereas alkali-based semiconducting photocathodes display a higher quantum efficiency (QE) in the visible light spectrum than their metallic counterparts, their lifetimes are much shorter due to the high reactivity of alkali-based surfaces to the residual gases in the vacuum chamber. Overcoming the tradeoff between QE and lifetimes has been a great challenge in the accelerator community. Herein, based on ab initio density functional calculations, we propose an approach to overcome this tradeoff by coating with atomically thin two-dimensional (2D) nanomaterials. On one hand, the 2D coating layers can enhance the lifetimes of photocathodes by preventing the chemical reactions with the residual gases. On the other hand, the 2D coating layers can effectively engineer the work function of photocathodes, thus controlling their QE. A monolayer of insulating BN reduces the work function, whereas a monolayer of semi-metallic graphene or semiconducting molybdenum disulfide (MoS2) increases the work function. This phenomenon originates from the induced interfacial dipoles. The reduction of work function by BN implies that it is capable of maintaining the high QE of semiconducting photocathodes in addition to enhance their lifetimes. This study advances our understandings on the surface chemistry of coated photocathodes and opens new technological avenues to fabricate photocathodes with high QE and longer lifetimes.
Individual Brain Charting, a high-resolution fMRI dataset for cognitive mapping
Authors: Pinho Ana Luísa , Amadon Alexis , Ruest Torsten , Fabre Murielle , Dohmatob Elvis , Denghien Isabelle , Ginisty Chantal , Becuwe-Desmidt Séverine , Roger Séverine , Laurier Laurence , Joly-Testault Véronique , Médiouni-Cloarec Gaëlle , Doublé Christine , Martins Bernadette , Pinel Philippe , Eger Evelyn , Varoquaux Gaël , Pallier Christophe , Dehaene Stanislas , Hertz-Pannier Lucie , Thirion Bertrand
Published: June 2018

Functional Magnetic Resonance Imaging (fMRI) has furthered brain mapping on perceptual, motor, as well as higher-level cognitive functions. However, to date, no data collection has systematically addressed the functional mapping of cognitive mechanisms at a fine spatial scale. The Individual Brain Charting (IBC) project stands for a high-resolution multi-task fMRI dataset that intends to provide the objective basis toward a comprehensive functional atlas of the human brain. The data refer to a cohort of 12 participants performing many different tasks. The large amount of task-fMRI data on the same subjects yields a precise mapping of the underlying functions, free from both inter-subject and inter-site variability. The present article gives a detailed description of the first release of the IBC dataset. It comprises a dozen of tasks, addressing both low- and high- level cognitive functions. This openly available dataset is thus intended to become a reference for cognitive brain mapping.
Fragmentation pattern of amides by EI and HRESI: study of protonation sites using DFT-3LYP data
Authors: Fokoue H. H. , Marques J. V. , Correia M. V. , Yamaguchi L. F. , Qu X. , Aires-de-Sousa J. , Scotti M. T. , Lopes N. P. , Kato M. J.
Published: June 2018

The N–CO cleavage of α,β-unsaturated piperamides under EI and ESI is supported by computational studies.
An interdigitated electrode with dense carbon nanotube forests on conductive supports for electrochemical biosensors
Authors: Sugime Hisashi , Ushiyama Takuya , Nishimura Keita , Ohno Yutaka , Noda Suguru
Published: June 2018

A highly sensitive interdigitated electrode (IDE) with vertically aligned dense carbon nanotube forests directly grown on conductive supports was demonstrated by combining UV lithography and a low temperature chemical vapor deposition process (470 °C).
Optical assays based on colloidal inorganic nanoparticles
Authors: Ghasemi Amir , Rabiee Navid , Ahmadi Sepideh , Hashemzadeh Shabnam , Lolasi Farshad , Bozorgomid Mahnaz , Kalbasi Alireza , Nasseri Behzad , Shiralizadeh Dezfuli Amin , Aref Amir Reza , Karimi Mahdi , Hamblin Michael R.
Published: June 2018

Colloidal inorganic nanoparticles have wide applications in the detection of analytes and in biological assays.
A robust fluorescent probe for detection of telomerase activityin vitroand imaging in living cellsviatelomerase-triggering primer extension to desorb DNA from graphene oxide
Authors: Gao Fenglei , Yao Yao , Wu Jing , Cui Lin , Zhang Yu , Geng Deqin , Tang Daoquan , Yu Yanyan
Published: June 2018

A novel strategy for telomerase imaging was developed based on telomerase-triggering primer extension to desorb fluorophore labeled DNA from graphene oxide.
Mercapto-modified magnesium silicate micro-particles for efficient extraction and preconcentration of mercury ions from estuary waters
Authors: Sajedifard Morteza , Ghanemi Kamal , Nickpour Yadollah
Published: June 2018

A quick, facile, and straightforward preconcentration technique based on the modification of magnesium silicate with mercapto-based ligands for sub-ppb determination of mercury ions in coastal seawaters.
PA/US dual-modality imaging to guide VEGFR-2 targeted photothermal therapy using ZnPc-/PFH-loaded polymeric nanoparticles
Authors: Chen Yu-li , Liu Feng-qiu , Guo Yuan , Cheng Juan , Yang Lu , Lu Min , Li Pan , Xu Jie , Yu Tao , Wang Zhi-gang , Cao Yang , Ran Hai-tao
Published: June 2018

Angiogenesis is a common pathological characteristic of many solid tumors and vulnerable atherosclerotic plaques.
Black TiO2-based nanoprobes for T1-weighted MRI-guided photothermal therapy in CD133 high expressed pancreatic cancer stem-like cells
Authors: Wang Siqi , Ren Wenzhi , Wang Jianhua , Jiang Zhenqi , Saeed Madiha , Zhang Lili , Li Aiguo , Wu Aiguo
Published: June 2018

New type of black TiO2 nanoprobes with high long relaxation rate and significant targeting capability were prepared for magnetic resonance imaging guided photothermal therapy in pancreatic stem-like cells.
PVP-assisted transformation of a metal–organic framework into Co-embedded N-enriched meso/microporous carbon materials as bifunctional electrocatalysts
Authors: Liang Zuozhong , Zhang Chaochao , Yuan Haitao , Zhang Wei , Zheng Haoquan , Cao Rui
Published: June 2018

A PVP-assisted pyrolysis strategy that can simply but efficiently transform zeolitic imidazolate framework-67 (ZIF-67) into a Co-embedded N-enriched meso/microporous carbon material (Co-NC) is reported for the first time.