bluuebunny/crossref_metadata_2025 huggingface dataset:
Zebrafish cyclin Dx is required for development of motor neuron progenitors and its expression is regulated by hypoxia-inducible factor 2α
Authors: Lien Huang-Wei , Yuan Rey-Yue , Chou Chih-Ming , Chen Yi-Chung , Hung Chin-Chun , Hu Chin-Hwa , Hwang Sheng-Ping L. , Hwang Pung-Pung , Shen Chia-Ning , Chen Chih-Lung , Cheng Chia-Hsiung , Huang Chang-Jen
Published: June 2016

Cyclins play a central role in cell-cycle regulation; in mammals, the D family of cyclins consists of cyclin D1, D2 and D3. In Xenopus, only homologs of cyclins D1 and D2 have been reported, while a novel cyclin, cyclin Dx (ccndx), was found to be required for the maintenance of motor neuron progenitors during embryogenesis. It remains unknown whether zebrafish possess cyclin D3 or cyclin Dx. In this study, we identified a zebrafish ccndx gene encoding a protein which can form a complex with Cdk4. Through whole-mount in situ hybridization, we observed that zccndx mRNA is expressed in the motor neurons of hindbrain and spinal cord during development. Analysis of a 4-kb promoter sequence of the zccndx gene revealed the presence of HRE sites, which can be regulated by HIF2α. Morpholino knockdown of zebrafish Hif2α and cyclin Dx resulted in the abolishment of isl1 and oligo2 expression in the precursors of motor neurons and also disrupted axon growth. Overexpression of cyclin Dx mRNA in Hif2α morphants partially rescued zccndx expression. Taken together, our data indicate that zebrafish cyclin Dx plays a role in maintaining the precursors of motor neurons.
Overexpression of the brassinosteroid biosynthetic gene DWF4 in Brassica napus simultaneously increases seed yield and stress tolerance
Authors: Sahni Sangita , Prasad Bishun D. , Liu Qing , Grbic Vojislava , Sharpe Andrew , Singh Surinder P. , Krishna Priti
Published: June 2016

As a resource allocation strategy, plant growth and defense responses are generally mutually antagonistic. Brassinosteroid (BR) regulates many aspects of plant development and stress responses, however, genetic evidence of its integrated effects on plant growth and stress tolerance is lacking. We overexpressed the Arabidopsis BR biosynthetic gene AtDWF4 in the oilseed plant Brassica napus and scored growth and stress response phenotypes. The transgenic B. napus plants, in comparison to wild type, displayed increased seed yield leading to increased overall oil content per plant, higher root biomass and root length, significantly better tolerance to dehydration and heat stress and enhanced resistance to necrotrophic fungal pathogens Leptosphaeria maculans and Sclerotinia sclerotiorum. Transcriptome analysis supported the integrated effects of BR on growth and stress responses; in addition to BR responses associated with growth, a predominant plant defense signature, likely mediated by BES1/BZR1, was evident in the transgenic plants. These results establish that BR can interactively and simultaneously enhance abiotic and biotic stress tolerance and plant productivity. The ability to confer pleiotropic beneficial effects that are associated with different agronomic traits suggests that BR–related genes may be important targets for simultaneously increasing plant productivity and performance under stress conditions.
Metal-free carbon nanotubes: synthesis, and enhanced intrinsic microwave absorption properties
Authors: Qi Xiaosi , Xu Jianle , Hu Qi , Deng Yu , Xie Ren , Jiang Yang , Zhong Wei , Du Youwei
Published: June 2016

In order to clearly understand the intrinsic microwave absorption properties of carbon nanomaterials, we proposed an efficient strategy to synthesize high purity metal-free carbon nanotubes (CNTs) over water-soluble K2CO3 particles through chemical vapor decomposition and water-washing process. The comparison results indicated the leftover catalyst caused negative effects in intrinsic microwave absorption properties of CNTs, while an enhanced microwave absorption performance could be observed over the metal-free CNT sample. Moreover, the results indicated that the microwave absorption properties could be tuned by the CNT content. Therefore, we provided a simple route to investigate the intrinsic properties of CNTs and a possible enhanced microwave absorbing mechanism.
Josephson effects in the junction formed by DIII-class topological and s-wave superconductors with an embedded quantum dot
Authors: Gao Zhen , Wang Xiao-Qi , Shan Wan-Fei , Wu Hai-Na , Gong Wei-Jiang
Published: June 2016

We investigate the Josephson effects in the junction formed by the indirect coupling between DIII-class topological and s-wave superconductors via an embedded quantum dot. Due to the presence of two kinds of superconductors, three dot-superconductor coupling manners are considered, respectively. As a result, the Josephson current is found to oscillate in period 2π. More importantly, the presence of Majorana doublet in the DIII-class superconductor renders the current finite at the case of zero phase difference, with its sign determined by the fermion parity of such a junction. In addition, the dot-superconductor coupling plays a nontrivial role in adjusting the Josephson current. When the s-wave superconductor couples to the dot in the weak limit, the current direction will have an opportunity to reverse. It is believed that these results will be helpful for understanding the transport properties of the DIII-class superconductor.
Multiple specialised goose-type lysozymes potentially compensate for an exceptional lack of chicken-type lysozymes in Atlantic cod
Authors: Seppola Marit , Bakkemo Kathrine Ryvold , Mikkelsen Helene , Myrnes Bjørnar , Helland Ronny , Irwin David M. , Nilsen Inge W.
Published: June 2016

Previous analyses of the Atlantic cod genome showed unique combinations of lacking and expanded number of genes for the immune system. The present study examined lysozyme activity, lysozyme gene distribution and expression in cod. Enzymatic assays employing specific bacterial lysozyme inhibitors provided evidence for presence of g-type, but unexpectedly not for c-type lysozyme activity. Database homology searches failed to identify any c-type lysozyme gene in the cod genome or in expressed sequence tags from cod. In contrast, we identified four g-type lysozyme genes (LygF1a-d) constitutively expressed, although differentially, in all cod organs examined. The active site glutamate residue is replaced by alanine in LygF1a, thus making it enzymatic inactive, while LygF1d was found in two active site variants carrying alanine or glutamate, respectively.In vitroandin vivoinfection by the intracellular bacteriumFrancisella noatunensisgave a significantly reduced LygF1a and b expression but increased expression of the LygF1c and d genes as did also the interferon gamma (IFNγ) cytokine. These results demonstrate a lack of c-type lysozyme that is unprecedented among vertebrates. Our results further indicate that serial gene duplications have produced multiple differentially regulated cod g-type lysozymes with specialised functions potentially compensating for the lack of c-type lysozymes.
Transformed MDCK cells secrete elevated MMP1 that generates LAMA5 fragments promoting endothelial cell angiogenesis
Authors: Gopal Shashi K. , Greening David W. , Zhu Hong-Jian , Simpson Richard J. , Mathias Rommel A.
Published: June 2016

Epithelial-mesenchymal transition (EMT) enhances the migration and invasion of cancer cells and is regulated by various molecular mechanisms including extracellular matrix metalloproteinase (MMP) activity. Previously, we reported transformation of epithelial Madin-Darby canine kidney (MDCK) cells with oncogenic H-Ras (21D1 cells) induces EMT and significantly elevates MMP1 expression. To explore the biological significance, in this study we characterized 21D1 cells with knocked-down MMP1 expression (21D1−MMP1). MMP1 silencing diminished 21D1 cell migration, invasion and anchorage-independent growth in vitro. Additionally, 21D1−MMP1 cells displayed reduced tumour volume when grown as in vivo subcutaneous xenografts in mice. Depletion of MMP1 lowered the ability of the cellular secretome (extracellular culture medium) to influence recipient cell behaviour. For example, supplementation with 21D1 secretome elevated cell migration of recipient fibroblasts and enhanced endothelial cell angiogenesis (vessel length and branching). By contrast, 21D1−MMP1 secretome was less potent in both functional assays. We reveal laminin subunit alpha-5 (LAMA5) as a novel biological substrate of MMP1, that generates internal and C-terminal proteolytic fragments in 21D1 secretome. Furthermore, antibody-based inhibition of integrin αvβ3 on endothelial cells nullified the angiogenic capability of 21D1 secretome. Therefore, we report this as a new VEGF-independent mechanism that oncogenic cells may employ to promote tumour angiogenesis.
Multifunctional Fe3O4 @ Au core/shell nanostars: a unique platform for multimode imaging and photothermal therapy of tumors
Authors: Hu Yong , Wang Ruizhi , Wang Shige , Ding Ling , Li Jingchao , Luo Yu , Wang Xiaolin , Shen Mingwu , Shi Xiangyang
Published: June 2016

We herein report the development of multifunctional folic acid (FA)-targeted Fe3O4 @ Au nanostars (NSs) for targeted multi-mode magnetic resonance (MR)/computed tomography (CT)/photoacoustic (PA) imaging and photothermal therapy (PTT) of tumors. In this present work, citric acid-stabilized Fe3O4/Ag composite nanoparticles prepared by a mild reduction route were utilized as seeds and exposed to the Au growth solution to induce the formation of Fe3O4 @ Au core/shell NSs. Followed by successive decoration of thiolated polyethyleneimine (PEI-SH), FA via a polyethylene glycol spacer and acetylation of the residual PEI amines, multifunctional Fe3O4 @ Au NSs were formed. The designed multifunctional NSs possess excellent colloidal stability, good cytocompatibility in a given concentration range and specific recognition to cancer cells overexpressing FA receptors. Due to co-existence of Fe3O4 core and star-shaped Au shell, the NSs can be used for MR and CT imaging of tumors, respectively. Likewise, the near infrared plasmonic absorption feature also enables the NSs to be used for PA imaging and PTT of tumors. Our study clearly demonstrates a unique theranostic nanoplatform that can be used for high performance multi-mode imaging-guided PTT of tumors, which may be extendable for theranostics of different diseases in translational medicine.
Approaching Defect-free Amorphous Silicon Nitride by Plasma-assisted Atomic Beam Deposition for High Performance Gate Dielectric
Authors: Tsai Shu-Ju , Wang Chiang-Lun , Lee Hung-Chun , Lin Chun-Yeh , Chen Jhih-Wei , Shiu Hong-Wei , Chang Lo-Yueh , Hsueh Han-Ting , Chen Hung-Ying , Tsai Jyun-Yu , Lu Ying-Hsin , Chang Ting-Chang , Tu Li-Wei , Teng Hsisheng , Chen Yi-Chun , Chen Chia-Hao , Wu Chung-Lin
Published: June 2016

In the past few decades, gate insulators with a high dielectric constant (high-k dielectric) enabling a physically thick but dielectrically thin insulating layer, have been used to replace traditional SiOx insulator and to ensure continuous downscaling of Si-based transistor technology. However, due to the non-silicon derivative natures of the high-k metal oxides, transport properties in these dielectrics are still limited by various structural defects on the hetero-interfaces and inside the dielectrics. Here, we show that another insulating silicon compound, amorphous silicon nitride (a-Si3N4), is a promising candidate of effective electrical insulator for use as a high-k dielectric. We have examined a-Si3N4 deposited using the plasma-assisted atomic beam deposition (PA-ABD) technique in an ultra-high vacuum (UHV) environment and demonstrated the absence of defect-related luminescence; it was also found that the electronic structure across the a-Si3N4/Si heterojunction approaches the intrinsic limit, which exhibits large band gap energy and valence band offset. We demonstrate that charge transport properties in the metal/a-Si3N4/Si (MNS) structures approach defect-free limits with a large breakdown field and a low leakage current. Using PA-ABD, our results suggest a general strategy to markedly improve the performance of gate dielectric using a nearly defect-free insulator.
EMMPRIN Down-regulating miR-106a/b Modifies Breast Cancer Stem-like Cell Properties via Interaction with Fibroblasts Through STAT3 and HIF-1α
Authors: Liu Yonglei , Zhang Jingling , Sun Xiangjun , Li Meilin
Published: June 2016

Extracellular matrix metalloproteinase inducer (EMMPRIN) is a heavily glycosylated protein and expresses in cancer cells widely, which plays important roles in tumor progression. However, the role of EMMPRIN in breast cancer stem-like cell properties by interaction with fibroblasts is not known. In the present study, we investigated the effects of fibroblasts on breast cancer stem-like cells. We found that fibroblasts activated by co-cultured breast cancer cells produced higher levels of EMMPRIN, which stimulated the stem-like cell specific, self-renewal and sphere-forming phenotype in breast cancer cells. Increased EMMPRIN expression in activated fibroblasts increased the expression of STAT3 and HIF-1α and showed cancer stem-like cell features in breast cancer cells. We also found that EMMPRIN could down-regulate miR-106a and miR-106b expression in breast cancer cells, which led to activating STAT3 and enhancing HIF-1α expression. Our results illustrated that EMMPRIN has an important role in breast cancer stem-like cells by activation STAT3/HIF-1α through interaction with cancer cells and fibroblasts. The study for the first time indicated that cancer cells and fibroblasts interaction promotes breast cancer cells showing stem-like cells through up-regulation EMMPRIN and led to inhibiting miR-106a/b expression which targets both STAT3 and HIF-1α expression.
Tunable electronic properties of graphene through controlling bonding configurations of doped nitrogen atoms
Authors: Zhang Jia , Zhao Chao , Liu Na , Zhang Huanxi , Liu Jingjing , Fu Yong Qing , Guo Bin , Wang Zhenlong , Lei Shengbin , Hu PingAn
Published: June 2016

Single–layer and mono–component doped graphene is a crucial platform for a better understanding of the relationship between its intrinsic electronic properties and atomic bonding configurations. Large–scale doped graphene films dominated with graphitic nitrogen (GG) or pyrrolic nitrogen (PG) were synthesized on Cu foils via a free radical reaction at growth temperatures of 230–300 °C and 400–600 °C, respectively. The bonding configurations of N atoms in the graphene lattices were controlled through reaction temperature and characterized using Raman spectroscopy, X–ray photoelectron spectroscopy and scanning tunneling microscope. The GG exhibited a strong n–type doping behavior, whereas the PG showed a weak n–type doping behavior. Electron mobilities of the GG and PG were in the range of 80.1–340 cm2 V−1·s−1 and 59.3–160.6 cm2 V−1·s−1, respectively. The enhanced doping effect caused by graphitic nitrogen in the GG produced an asymmetry electron–hole transport characteristic, indicating that the long–range scattering (ionized impurities) plays an important role in determining the carrier transport behavior. Analysis of temperature dependent conductance showed that the carrier transport mechanism in the GG was thermal excitation, whereas that in the PG, was a combination of thermal excitation and variable range hopping.
Record dry summer in 2015 challenges precipitation projections in Central Europe
Authors: Orth René , Zscheischler Jakob , Seneviratne Sonia I.
Published: June 2016

Central Europe was characterized by a humid-temperate climate in the 20th century. Climate change projections suggest that climate in this area will shift towards warmer temperatures by the end of the 21st century, while projected precipitation changes are highly uncertain. Here we show that the 2015 summer rainfall was the lowest on record since 1901 in Central Europe and that climate models that perform best in the three driest years of the historical time period 1901–2015 project stronger drying trends in the 21st century than models that perform best in the remaining years. Analyses of precipitation and derived soil moisture reveal that the 2015 event was drier than both the recent 2003 or 2010 extreme summers in Central Europe. Additionally there are large anomalies in satellite-derived vegetation greenness. In terms of precipitation and temperature anomalies, the 2015 summer in Central Europe is found to lie between historical climate in the region and that characteristic of the Mediterranean area. Even though the models best capturing past droughts are not necessarily generally more reliable in the future, the 2015 drought event illustrates that potential future drying trends have severe implications and could be stronger than commonly assumed from the entire IPCC AR5 model ensemble.
Enhanced Ghrelin Levels and Hypothalamic Orexigenic AgRP and NPY Neuropeptide Expression in Models of Jejuno-Colonic Short Bowel Syndrome
Authors: Gillard Laura , Billiauws Lore , Stan-Iuga Bogdan , Ribeiro-Parenti Lara , Jarry Anne-Charlotte , Cavin Jean-Baptiste , Cluzeaud Françoise , Mayeur Camille , Thomas Muriel , Freund Jean-Noël , Lacorte Jean-Marc , Le Gall Maude , Bado André , Joly Francisca , Le Beyec Johanne
Published: June 2016

Short bowel syndrome (SBS) patients developing hyperphagia have a better outcome. Gastrointestinal endocrine adaptations help to improve intestinal functions and food behaviour. We investigated neuroendocrine adaptations in SBS patients and rat models with jejuno-ileal (IR-JI) or jejuno-colonic (IR-JC) anastomosis with and without parenteral nutrition. Circulating levels of ghrelin, PYY, GLP-1, and GLP-2 were determined in SBS rat models and patients. Levels of mRNA for proglucagon, PYY and for hypothalamic neuropeptides were quantified by qRT-PCR in SBS rat models. Histology and immunostaining for Ki67, GLP-1 and PYY were performed in SBS rats. IR-JC rats, but not IR-JI, exhibited significantly higher crypt depths and number of Ki67-positive cells than sham. Fasting and/or postprandial plasma ghrelin and PYY concentrations were higher, or tend to be higher, in IR-JC rats and SBS-JC patients than in controls. Proglucagon and Pyy mRNA levels were significantly enhanced in IR-JC rats. Levels of mRNA coding hypothalamic orexigenic NPY and AgRP peptides were significantly higher in IR-JC than in sham rats. We demonstrate an increase of plasma ghrelin concentrations, major changes in hypothalamic neuropeptides levels and greater induction of PYY in SBS-JC rats and patients suggesting that jejuno-colonic continuity creates a peculiar environment promoting further gut-brain adaptations.
Water-soluble benzylidene cyclopentanone based photosensitizers for in vitro and in vivo antimicrobial photodynamic therapy
Authors: Fang Yanyan , Liu Tianlong , Zou Qianli , Zhao Yuxia , Wu Feipeng
Published: June 2016

Antimicrobial photodynamic therapy (aPDT) has been proposed to cope with the increasing antibiotic resistance among pathogens. As versatile pharmacophores, benzylidene cyclopentanone based photosensitizers (PSs) have been used in various bioactive materials. However, their reports as aPDT agents are very limited, and relationships between their chemical structures and antibacterial abilities have not been systematically discussed. Here, nine water-soluble benzylidene cyclopentanone PSs modified by polyethylene glycol (PEG), carboxylate anionic or pyridyl cationic agents are studied for aPDT. It is found that the binding/uptake abilities and aPDT effects of these PSs toward bacterial cells vary significantly when adjusting the number and position of their terminal charged groups. Though the comparable (also best) binding/uptake amounts are achieved by both cationic PS P3 and anionic PS Y1, only Y1 exhibits much more excellent aPDT activities than other PSs. Antibacterial mechanisms reveal that, relative to the favorable cell wall-binding of cationic PS P3, the anionic PS Y1 can accumulate more in the spheroplast/protoplast of methicillin-resistant Staphylococcus aureus (MRSA), which ensures its high efficient aPDT abilities both in vitro and in vivo. This study suggests the great clinical application potential of Y1 in inactivation of MRSA.
An interpolatory ansatz captures the physics of one-dimensional confined Fermi systems
Authors: Andersen M. E. S. , Dehkharghani A. S. , Volosniev A. G. , Lindgren E. J. , Zinner N. T.
Published: June 2016

Interacting one-dimensional quantum systems play a pivotal role in physics. Exact solutions can be obtained for the homogeneous case using the Bethe ansatz and bosonisation techniques. However, these approaches are not applicable when external confinement is present. Recent theoretical advances beyond the Bethe ansatz and bosonisation allow us to predict the behaviour of one-dimensional confined systems with strong short-range interactions and new experiments with cold atomic Fermi gases have already confirmed these theories. Here we demonstrate that a simple linear combination of the strongly interacting solution with the well-known solution in the limit of vanishing interactions provides a simple and accurate description of the system for all values of the interaction strength. This indicates that one can indeed capture the physics of confined one-dimensional systems by knowledge of the limits using wave functions that are much easier to handle than the output of typical numerical approaches. We demonstrate our scheme for experimentally relevant systems with up to six particles. Moreover, we show that our method works also in the case of mixed systems of particles with different masses. This is an important feature because these systems are known to be non-integrable and thus not solvable by the Bethe ansatz technique.
Electrically switchable organo–inorganic hybrid for a white-light laser source
Authors: Huang Jui-Chieh , Hsiao Yu-Cheng , Lin Yu-Ting , Lee Chia-Rong , Lee Wei
Published: June 2016

We demonstrate a spectrally discrete white-light laser device based on a photonic bandgap hybrid, which is composed of a soft photonic crystal; i.e., a layer of dye-doped cholesteric liquid crystal (CLC), sandwiched between two imperfect but identical, inorganic multilayer photonic crystals. With a sole optical pump, a mono-, bi-, or tri-chromatic laser can be obtained and, through the soft photonic crystal regulated by an applied voltage, the hybrid possesses electrical tunability in laser wavelength. The three emitted spectral peaks originate from two bandedges of the CLC reflection band as well as one of the photonic defect modes in dual-mode lasing. Thanks to the optically bistable nature of CLC, such a white-light laser device can operate in quite an energy-saving fashion. This technique has potential to fulfill the present mainstream in the coherent white-light source.
Soil fungal community comparison of different mulberry genotypes and the relationship with mulberry fruit sclerotiniosis
Authors: Yu Cui , Hu Xingming , Deng Wen , Li Yong , Han Guangming , Ye Chuhua
Published: June 2016

Mulberry fruit sclerotiniosis is a common soil-borne disease. We hypothesize that there is a relationship between the incidence of mulberry fruit sclerotiniosis and the soil fungal community. Therefore four mulberry genotypes with different resistance to sclerotiniosis were selected to study their soil fungal community under the same condition. A total of 6 phyla and 93 genera were identified from all mulberry samples. Genera affected by genotype, cover, and genotype by cover interactions, were 23, 20, and 11, respectively. There were 10 genera that differed between the resistant cultivars and the susceptible cultivars. In addition, the relative abundances of Humicola and Mortierella in the resistant mulberry cultivars with the cover treatments were significantly higher than that of in the susceptible cultivars. However, the relative abundance of Sclerotiniaceae and Scleromitrula that may cause sclerotiniosis in the uncover treatments were significantly higher compared with the cover treatments. The results suggested that the genotype of mulberry has a significant impact on the soil microbial community that may result in differences in resistance to sclerotiniosis, and covering could reduce the relative abundance of Sclerotiniaceae or Scleromitrula.
The impact of simulated MRI scanner background noise on visual attention processes as measured by the EEG
Authors: Kobald S. Oliver , Getzmann Stephan , Beste Christian , Wascher Edmund
Published: June 2016

Environmental noise is known to affect personal well-being as well as cognitive processes. Besides daily life, environmental noise can also occur in experimental research settings, e.g. when being in a magnetic resonance scanner. Scanner background noise (SBN) might pose serious confounds for experimental findings, even when non-auditory settings are examined. In the current experiment we tested if SBN alters bottom-up and top-down related processes of selective visual attention mechanisms. Participants completed two blocks of a visual change detection task, one block in silence and one block under SBN exposure. SBN was found to decrease accuracy in measures of visual attention. This effect was modulated by the temporal occurrence of SBN. When SBN was encountered in the first block, it prevented a significant improvement of accuracy in the second block. When SBN appeared in the second block, it significantly decreased accuracy. Neurophysiological findings showed a strong frontal positivity shift only when SBN was present in the first block, suggesting an inhibitory process to counteract the interfering SBN. Common correlates of both top-down and bottom-up processes of selective visual attention were not specifically affected by SBN exposure. Further research appears necessary to entirely rule out confounds of SBN in assessing visual attention.
Dual Drug Loaded Biodegradable Nanofibrous Microsphere for Improving Anti-Colon Cancer Activity
Authors: Fan Rangrang , Li Xiaoling , Deng Jiaojiao , Gao Xiang , Zhou Liangxue , Zheng Yu , Tong Aiping , Zhang Xiaoning , You Chao , Guo Gang
Published: June 2016

One of the approaches being explored to increase antitumor activity of chemotherapeutics is to inject drug-loaded microspheres locally to specific anatomic sites, providing for a slow, long term release of a chemotherapeutic while minimizing systemic exposure. However, the used clinically drug carriers available at present have limitations, such as their low stability, renal clearance and residual surfactant. Here, we report docetaxel (DOC) and curcumin (CUR) loaded nanofibrous microspheres (DOC + CUR/nanofibrous microspheres), self-assembled from biodegradable PLA-PEO-PPO-PEO-PLA polymers as an injectable drug carrier without adding surfactant during the emulsification process. The obtained nanofibrous microspheres are composed entirely of nanofibers and have an open hole on the shell without the assistance of a template. It was shown that these DOC + CUR/nanofibrous microspheres could release curcumin and docetaxel slowly in vitro. The slow, sustained release of curcumin and docetaxel in vivo may help maintain local concentrations of active drug. The mechanism by which DOC + CUR/nanofibrous microspheres inhibit colorectal peritoneal carcinomatosis might involve increased induction of apoptosis in tumor cells and inhibition of tumor angiogenesis. In vitro and in vivo evaluations demonstrated efficacious synergistic antitumor effects against CT26 of curcumin and docetaxel combined nanofibrous microspheres. In conclusion, the dual drug loaded nanofibrous microspheres were considered potentially useful for treating abdominal metastases of colorectal cancer.
Altered multisensory temporal integration in obesity
Authors: Scarpina Federica , Migliorati Daniele , Marzullo Paolo , Mauro Alessandro , Scacchi Massimo , Costantini Marcello
Published: June 2016

Eating is a multisensory behavior. The act of placing food in the mouth provides us with a variety of sensory information, including gustatory, olfactory, somatosensory, visual and auditory. Evidence suggests altered eating behavior in obesity. Nonetheless, multisensory integration in obesity has been scantily investigated so far. Starting from this gap in the literature, we seek to provide the first comprehensive investigation of multisensory integration in obesity. Twenty male obese participants and twenty male healthy-weight participants took part in the study aimed at describing the multisensory temporal binding window (TBW). The TBW is defined as the range of stimulus onset asynchrony in which multiple sensory inputs have a high probability of being integrated. To investigate possible multisensory temporal processing deficits in obesity, we investigated performance in two multisensory audiovisual temporal tasks, namely simultaneity judgment and temporal order judgment. Results showed a wider TBW in obese participants as compared to healthy-weight controls. This holds true for both the simultaneity judgment and the temporal order judgment tasks. An explanatory hypothesis would regard the effect of metabolic alterations and low-grade inflammatory state, clinically observed in obesity, on the temporal organization of brain ongoing activity, which one of the neural mechanisms enabling multisensory integration.
MDCK cells expressing constitutively active Yes-associated protein (YAP) undergo apical extrusion depending on neighboring cell status
Authors: Chiba Takanori , Ishihara Erika , Miyamura Norio , Narumi Rika , Kajita Mihoko , Fujita Yasuyuki , Suzuki Akira , Ogawa Yoshihiro , Nishina Hiroshi
Published: June 2016

Cell competition is a cell-cell interaction by which a cell compares its fitness to that of neighboring cells. The cell with the relatively lower fitness level is the “loser” and actively eliminated, while the cell with the relatively higher fitness level is the “winner” and survives. Recent studies have shown that cells with high Yes-associated protein (YAP) activity win cell competitions but the mechanism is unknown. Here, we report the unexpected finding that cells overexpressing constitutively active YAP undergo apical extrusion and are losers, rather than winners, in competitions with normal mammalian epithelial cells. Inhibitors of metabolism-related proteins such as phosphoinositide-3-kinase (PI3K), mammalian target of rapamycin (mTOR), or p70S6 kinase (p70S6K) suppressed this apical extrusion, as did knockdown of vimentin or filamin in neighboring cells. Interestingly, YAP-overexpressing cells switched from losers to winners when co-cultured with cells expressing K-Ras (G12V) or v-Src. Thus, the role of YAP in deciding cell competitions depends on metabolic factors and the status of neighboring cells.
Down-regulation of HSP60 Suppresses the Proliferation of Glioblastoma Cells via the ROS/AMPK/mTOR Pathway
Authors: Tang Haiping , Li Jin , Liu Xiaohui , Wang Guihuai , Luo Minkui , Deng Haiteng
Published: June 2016

Glioblastoma is a fatal and incurable cancer with the hyper-activated mTOR pathway. HSP60, a major chaperone for maintenance of mitochondrial proteostasis, is highly expressed in glioblastoma patients. To understand the effects of HSP60 on glioblastoma tumorigenesis and progression, we characterized the HSP60-knockdowned glioblastoma cells and revealed that HSP60 silencing markedly suppressed cell proliferation and promoted cell to undergo the epithelial-mesenchymal transition (EMT). Proteomic analysis showed that ribosomal proteins were significantly downregulated whereas EMT-associated proteins were up-regulated in HSP60-knockdowned U87 cells as confirmed by a distinct enrichment pattern in newly synthesized proteins with azido-homoalanine labeling. Biochemical analysis revealed that HSP60 knockdown increased reactive oxygen species (ROS) production that led to AMPK activation, similarly to the complex I inhibitor rotenone-induced AMPK activation. Activated AMPK suppressed mTORC1 mediated S6K and 4EBP1 phosphorylation to decrease protein translation, which slowed down cell growth and proliferation. On the other hand, high levels of ROS in HSP60 knockdowned or rotenone-treated U87 cells contributed to EMT. These results indicate that HSP60 silencing deactivates the mTOR pathway to suppress glioblastoma progression, suggesting that HSP60 is a potential therapeutic target for glioblastoma treatment.
Mechanochemical conversion of brominated POPs into useful oxybromides: a greener approach
Authors: Cagnetta Giovanni , Liu Han , Zhang Kunlun , Huang Jun , Wang Bin , Deng Shubo , Wang Yujue , Yu Gang
Published: June 2016

Brominated organic pollutants are considered of great concern for their adverse effect on human health and the environment, so an increasing number of such compounds are being classified as persistent organic pollutants (POPs). Mechanochemical destruction is a promising technology for POPs safe disposal because it can achieve their complete carbonization by solvent-free high energy ball milling at room temperature. However, a large amount of co-milling reagent usually is necessary, so a considerable volume of residue is produced. In the present study a different approach to POPs mechanochemical destruction is proposed. Employing stoichiometric quantities of Bi2O3 or La2O3 as co-milling reagent, brominated POPs are selectively and completely converted into their corresponding oxybromides (i.e. BiOBr and LaOBr), which possess very peculiar properties and can be used for some actual and many more potential applications. In this way, bromine is beneficially reused in the final product, while POPs carbon skeleton is safely destroyed to amorphous carbon. Moreover, mechanochemical destruction is employed in a greener and more sustainable manner.
Protection against doxorubicin-induced myocardial dysfunction in mice by cardiac-specific expression of carboxyl terminus of hsp70-interacting protein
Authors: Wang Lei , Zhang Tian-Peng , Zhang Yuan , Bi Hai-Lian , Guan Xu-Min , Wang Hong-Xia , Wang Xia , Du Jie , Xia Yun-Long , Li Hui-Hua
Published: June 2016

Carboxyl terminus of Hsp70-interacting protein (CHIP) is a critical ubiquitin ligase/cochaperone to reduce cardiac oxidative stress, inflammation, cardiomyocyte apoptosis and autophage etc. However, it is unclear whether overexpression of CHIP in the heart would exert protective effects against DOX-induced cardiomyopathy. Cardiac-specific CHIP transgenic (CHIP-TG) mice and the wild-type (WT) littermates were treated with DOX or saline. DOX-induced cardiac atrophy, dysfunction, inflammation, oxidative stress and cardiomyocyte apoptosis were significantly attenuated in CHIP-TG mice. CHIP-TG mice also showed higher survival rate than that of WT mice (40% versus 10%) after 10-day administration of DOX. In contrast, knockdown of CHIP by siRNA in vitro further enhanced DOX-induced cardiotoxic effects. Global gene microarray assay revealed that after DOX-treatment, differentially expressed genes between WT and CHIP-TG mice were mainly involved in apoptosis, atrophy, immune/inflammation and oxidative stress. Mechanistically, CHIP directly promotes ubiquitin-mediated degradation of p53 and SHP-1, which results in activation of ERK1/2 and STAT3 pathways thereby ameliorating DOX-induced cardiac toxicity.
Systematic protein interactome analysis of glycosaminoglycans revealed YcbS as a novel bacterial virulence factor
Authors: Hsiao Felix Shih-Hsiang , Sutandy FX Reymond , Syu Guan-Da , Chen Yi-Wen , Lin Jun-Mu , Chen Chien-Sheng
Published: June 2016

Microbial pathogens have evolved several strategies for interacting with host cell components, such as glycosaminoglycans (GAGs). Some microbial proteins involved in host–GAG binding have been described; however, a systematic study on microbial proteome–mammalian GAG interactions has not been conducted. Here, we usedEscherichia coliproteome chips to probe four typical mammalian GAGs, heparin, heparan sulphate (HS), chondroitin sulphate B (CSB) and chondroitin sulphate C (CSC) and identified 185 heparin-, 62 HS-, 98 CSB- and 101 CSC-interacting proteins. Bioinformatics analyses revealed the unique functions of heparin- and HS-specific interacting proteins in glycine, serine and threonine metabolism. Among all the GAG-interacting proteins, three were outer membrane proteins (MbhA, YcbS and YmgH). Invasion assays confirmed that mutantE. colilackingycbScould not invade the epithelial cells. Introducing plasmid carryingycbScomplemented the invading defects atycbSlackingE. colimutant, that can be further improved by overexpressingycbS. Preblocking epithelial cells with YcbS reduced the percentage ofE. coliinvasions. Moreover, we observed that whole components of theycboperon were crucial for invasion. The displacement assay revealed that YcbS binds to the laminin-binding site of heparin and might affect the host extracellular matrix structure by displacing heparin from laminin.
Roots of forbs sense climate fluctuations in the semi-arid Loess Plateau: Herb-chronology based analysis
Authors: Shi Songlin , Li Zongshan , Wang Hao , von Arx Georg , Lü Yihe , Wu Xing , Wang Xiaochun , Liu Guohua , Fu Bojie
Published: June 2016

Growth of herbaceous plants responds sensitively and rapidly to climate variability. Yet, little is known regarding how climate warming influences the growth of herbaceous plants, particularly in semi-arid sites. This contrasts with widely reported tree growth decline and even mortality in response to severe water deficits due to climate warming around the world. Here, we use the relatively novel approach of herb-chronology to analyze the correlation between climatic factors and annual ring width in the root xylem of two perennial forb species (Medicago sativa, Potentilla chinensis) in the Loess Plateau of China. We show that warming-induced water deficit has a significant negative effect on the growth of herbaceous plants in the Loess Plateau. Our results indicate that the growth of forbs responds rapidly and sensitively to drought variability, implying that water availability plays a dominant role in regulating the growth of herbaceous plants in semi-arid areas. If warming and drying in the Loess Plateau continue in the future, further affects the growth of herbaceous plants, potentially driving regional changes in the relationship between herbaceous vegetation and climate.
A new autoinhibited kinase conformation reveals a salt-bridge switch in kinase activation
Authors: Wei Qiang , Yang Shaoyuan , Li Dan , Zhang Xiaoying , Zheng Jimin , Jia Zongchao
Published: June 2016

In the structure of autoinhibited EphA2 tyrosine kinase reported herein, we have captured the entire activation segment, revealing a previously unknown role of the conserved Arg762 in kinase autoinhibition by interacting with the essential Mg2+-chelating Asp757. While it is well known that this Arg residue is involved in an electrostatic interaction with the phospho-residue of the activation loop to stabilize the active conformation, our structure determination revealed a new role for the Arg, acting as a switch between the autoinhibited and activated conformations. Mutation of Arg762 to Ala in EphA2 sensitized Mg2+ response, resulting in enhanced kinase catalytic activity and Mg2+ cooperativity. Furthermore, mutation of the corresponding Arg/Lys to Ala in PKA and p38MAPK also exhibited similar behavior. This new salt bridge-mediated switch may thus be an important mechanism of activation on a broader scope for kinases which utilize autophosphorylation.
Association between the ambient temperature and the occurrence of human Salmonella and Campylobacter infections
Authors: Yun Josef , Greiner Matthias , Höller Christiane , Messelhäusser Ute , Rampp Albert , Klein Günter
Published: June 2016

Salmonella spp. and thermotolerant Campylobacter spp. are the most important causes of human bacterial diarrheal infections worldwide. These bacterial species are influenced by several factors like behaviour of the host, shedding, environment incl. directly or indirectly through ambient temperature, and the infections show seasonality. Therefore, the aim of our study was to investigate the association between the occurrence of human campylobacteriosis and salmonellosis and the ambient temperature. The number of campylobacteriosis and salmonellosis cases in two German metropolises, Munich and Berlin, and three rural regions was analysed with simultaneous consideration of the ambient temperature over a period of four years (2001 to 2004) using regression, time series, and cross-correlation analysis. The statistical analysis showed that an increase in the ambient temperature correlated positively with an increase in human Salmonella and Campylobacter cases. The correlation occurred with a delay of approximately five weeks. The seasonal rise in ambient temperature correlated with increased incidence of bacterial diarrheal infections.
Study of antibacterial mechanism of graphene oxide using Raman spectroscopy
Authors: Nanda Sitansu Sekhar , Yi Dong Kee , Kim Kwangmeyung
Published: June 2016

Graphene oxide (GO) is extensively proposed as an effective antibacterial agent in commercial product packaging and for various biomedical applications. However, the antibacterial mode of action of GO is yet hypothetical and unclear. Here we developed a new and sensitive fingerprint approach to study the antibacterial activity of GO and underlying mechanism, using Raman spectroscopy. Spectroscopic signatures obtained from biomolecules such as Adenine and proteins from bacterial cultures with different concentrations of GO, allowed us to probe the antibacterial activity of GO with its mechanism at the molecular level. Escherichia coli (E. coli) and Enterococcus faecalis (E. faecalis) were used as model micro-organisms for all the experiments performed. The observation of higher intensity Raman peaks from Adenine and proteins in GO treated E. coli and E. faecalis; correlated with induced death, confirmed by Scanning electron Microscopy (SEM) and Biological Atomic Force Microscopy (Bio-AFM). Our findings open the way for future investigations of the antibacterial properties of different nanomaterial/GO composites using Raman spectroscopy.
Critical Role of COI1-Dependent Jasmonate Pathway in AAL toxin induced PCD in Tomato Revealed by Comparative Proteomics
Authors: Zhang Min , Koh Jin , Liu Lihong , Shao Zhiyong , Liu Haoran , Hu Songshen , Zhu Ning , Dufresne Craig P. , Chen Sixue , Wang Qiaomei
Published: June 2016

Alternaria alternata f.sp. Lycopersici (AAL) toxin induces programmed cell death (PCD) in susceptible tomato (Solanum lycopersicum) leaves. Jasmonate (JA) promotes AAL toxin induced PCD in a COI1 (coronatine insensitive 1, JA receptor)-dependent manner by enhancement of reactive oxygen species (ROS) production. To further elucidate the underlying mechanisms of this process, we performed a comparative proteomic analysis using tomato jasmonic acid insensitive1 ( jai1), the receptor mutant of JA, and its wild type (WT) after AAL toxin treatment with or without JA treatment. A total of 10367 proteins were identified in tomato leaves using isobaric tags for relative and absolute quantitation (iTRAQ) quantitative proteomics approach. 2670 proteins were determined to be differentially expressed in response to AAL toxin and JA. Comparison between AAL toxin treated jai1 and its WT revealed the COI1-dependent JA pathway regulated proteins, including pathways related to redox response, ceramide synthesis, JA, ethylene (ET), salicylic acid (SA) and abscisic acid (ABA) signaling. Autophagy, PCD and DNA damage related proteins were also identified. Our data suggest that COI1-dependent JA pathway enhances AAL toxin induced PCD through regulating the redox status of the leaves, other phytohormone pathways and/or important PCD components.
Removal of trace metal contaminants from potable water by electrocoagulation
Authors: Heffron Joe , Marhefke Matt , Mayer Brooke K.
Published: June 2016

This study investigated the effects of four operational and environmental variables on the removal of trace metal contaminants from drinking water by electrocoagulation (EC). Removal efficiencies for five metals (arsenic, cadmium, chromium, lead and nickel) were compared under varying combinations of electrode material, post-treatment, water composition and pH. Iron electrodes out-performed aluminum electrodes in removing chromium and arsenic. At pH 6.5, aluminum electrodes were slightly more effective at removing nickel and cadmium, while at pH 8.5, iron electrodes were more effective for these metals. Regardless of electrode, cadmium and nickel removal efficiencies were higher at pH 8.5 than at pH 6.5. Post-EC treatment using membrane filtration (0.45 μm) enhanced contaminant removal for all metals but nickel. With the exception of lead, all metals exhibited poorer removal efficiencies as the ionic strength of the background electrolyte increased, particularly in the very high-solids synthetic groundwaters. Residual aluminum concentrations were lowest at pH 6.5, while iron residuals were lowest in low ionic strength waters. Both aluminum and iron residuals required post-treatment filtration to meet drinking water standards. EC with post-treatment filtration appears to effectively remove trace metal contaminants to potable water standards, but both reactor and source water parameters critically impact removal efficiency.
Shear-banding Induced Indentation Size Effect in Metallic Glasses
Authors: Lu Y. M. , Sun B. A. , Zhao L. Z. , Wang W. H. , Pan M. X. , Liu C. T. , Yang Y.
Published: June 2016

Shear-banding is commonly regarded as the “plasticity carrier” of metallic glasses (MGs), which usually causes severe strain localization and catastrophic failure if unhindered. However, through the use of the high-throughput dynamic nanoindentation technique, here we reveal that nano-scale shear-banding in different MGs evolves from a “distributed” fashion to a “localized” mode when the resultant plastic flow extends over a critical length scale. Consequently, a pronounced indentation size effect arises from the distributed shear-banding but vanishes when shear-banding becomes localized. Based on the critical length scales obtained for a variety of MGs, we unveil an intrinsic interplay between elasticity and fragility that governs the nanoscale plasticity transition in MGs. Our current findings provide a quantitative insight into the indentation size effect and transition mechanisms of nano-scale plasticity in MGs.
The nucleotidohydrolases DCTPP1 and dUTPase are involved in the cellular response to decitabine
Authors: Requena Cristina E. , Pérez-Moreno Guiomar , Horváth András , Vértessy Beáta G. , Ruiz-Pérez Luis M. , González-Pacanowska Dolores , Vidal Antonio E.
Published: June 2016

Decitabine (5-aza-2′-deoxycytidine, aza-dCyd) is an anti-cancer drug used clinically for the treatment of myelodysplastic syndromes and acute myeloid leukaemia that can act as a DNA-demethylating or genotoxic agent in a dose-dependent manner. On the other hand, DCTPP1 (dCTP pyrophosphatase 1) and dUTPase are two ‘house-cleaning’ nucleotidohydrolases involved in the elimination of non-canonical nucleotides. In the present study, we show that exposure of HeLa cells to decitabine up-regulates the expression of several pyrimidine metabolic enzymes including DCTPP1, dUTPase, dCMP deaminase and thymidylate synthase, thus suggesting their contribution to the cellular response to this anti-cancer nucleoside. We present several lines of evidence supporting that, in addition to the formation of aza-dCTP (5-aza-2′-deoxycytidine-5′-triphosphate), an alternative cytotoxic mechanism for decitabine may involve the formation of aza-dUMP, a potential thymidylate synthase inhibitor. Indeed, dUTPase or DCTPP1 down-regulation enhanced the cytotoxic effect of decitabine producing an accumulation of nucleoside triphosphates containing uracil as well as uracil misincorporation and double-strand breaks in genomic DNA. Moreover, DCTPP1 hydrolyses the triphosphate form of decitabine with similar kinetic efficiency to its natural substrate dCTP and prevents decitabine-induced global DNA demethylation. The data suggest that the nucleotidohydrolases DCTPP1 and dUTPase are factors involved in the mode of action of decitabine with potential value as enzymatic targets to improve decitabine-based chemotherapy.