517 research outputs found

    Intranasal administration of endometrial mesenchymal stem cells as a suitable approach for Parkinson�s disease therapy

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    This study aimed to investigate the therapeutic effects of intranasal administration of human endometrium-derived stem cells (HEDSCs) in the mouse model of Parkinson�s disease (PD). Thirty days after intrastriatal injection of 6-OHDA, HEDSCs were administrated intranasally in three doses (104, 5 � 104 and 105 cells µl�1). During 120 days after stem cell administration, behavioral tests were examined. Then the mice were sacrificed and the fresh section of the substantia nigra pars compacta (SNpc) was used for detection of HEDSCs-GFP labeled by fluorescence microscopy method. In addition, immunohistochemistry was used to assay GFP, human neural Nestin, and tyrosine hydroxylase (TH) markers in the fixed brain tissue at the SNpc. Our data revealed that behavioral parameters were significantly improved after cell therapy. Fluorescence microscopy assay in fresh tissue and GFP analysis in fixed tissue were showed that the HEDSCs-GFP labeled migrated to SNpc. The data from immunohistochemistry revealed that the Nestin as a differential neuronal biomarker was expressed in SNpc. Also, TH as a dopaminergic neuron marker significantly increased after HEDSCs therapy in an optimized dose 5 � 104 cells µl�1. Our results suggest that intranasal administration of HEDSCs improve the PD symptoms in the mouse model of PD dose-dependent manner as a noninvasive method. © 2019, Springer Nature B.V

    Id1 Promotes Tumor Cell Migration in Nonsmall Cell Lung Cancers

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    Id1, which belongs to the Id family of helix-loop-helix transcription factors has been most associated with tumor progression and metastatsis; however, its significance in lung cancers has not been extensively explored. Here we seek to evaluate the expression of Id1 in a pilot study of nonsmall-cell lung cancers (NSCLCs) and determine its diagnostic and functional significance in these tumors. Paired normal and malignant lung tissues as well as a panel of NSCLC primary tumors and cell lines were evaluated for Id1 expression using Western blotting and quantitative RT-PCR. Functional assays were performed to evaluate the role of Id1 in tumor cell growth, migration and progression. We find Id1 expression is upregulated in squamous cell carcinoma when compared to adenocarcinoma of the lung and that expression of Id1 versus the normal control is variable in NSCLCs. We also note that Id1 expression in NSCLC cells is largely growth factor dependant and constitutive expression of Id1 in NSCLC cells significantly increases tumor cell migration without affecting cell proliferation. We conclude that Id1, as a mediator of tumor cell migration, may be an indicator of aggressive potential in nonsmall-cell lung cancers

    Biodegradable PLGA Based Nanoparticles for Sustained Regional Lymphatic Drug Delivery

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    The purpose of this work is to evaluate biodegradable drug carriers with defined size, hydrophobicity, and surface charge density for preferential lymphatic uptake and retention for sustained regional drug delivery. PLGA–PMA:PLA-PEG (PP) nanoparticles of defined size and relative hydrophobicity were prepared by nanoprecipitation method. These were compared with PS particles of similar sizes and higher hydrophobicity. PLGA–PMA:PLGA-COOH (PC) particles at 80:20, 50:50, and 20:80 ratios were prepared by nanoprecipitation for the charge study. Particle size and zeta potential were characterized by dynamic light scattering and laser doppler anemometry, respectively. Particles were administered in vivo to rats subcutaneously. Systemic and lymph node uptake was evaluated by marker recovery. Lymphatic uptake and node retention of PP nanoparticles was shown to be inversely related to size. Lymphatic uptake and node retention of PP particles, as compared to PS particles, was shown to be inversely related to hydrophobicity. Lastly, lymphatic uptake and node retention of PC nanoparticles were directly related to the anionic charge on the particles. In vivo lymphatic uptake and retention in a rat model indicates that the 50 nm PP particles are ideal for sustained regional delivery into the lymphatics for prevention/treatment of oligometastases

    On the emergent Semantic Web and overlooked issues

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    The emergent Semantic Web, despite being in its infancy, has already received a lotof attention from academia and industry. This resulted in an abundance of prototype systems and discussion most of which are centred around the underlying infrastructure. However, when we critically review the work done to date we realise that there is little discussion with respect to the vision of the Semantic Web. In particular, there is an observed dearth of discussion on how to deliver knowledge sharing in an environment such as the Semantic Web in effective and efficient manners. There are a lot of overlooked issues, associated with agents and trust to hidden assumptions made with respect to knowledge representation and robust reasoning in a distributed environment. These issues could potentially hinder further development if not considered at the early stages of designing Semantic Web systems. In this perspectives paper, we aim to help engineers and practitioners of the Semantic Web by raising awareness of these issues

    Simple broadband circularly polarized monopole antenna with two asymmetrically connected U-shaped parasitic strips and defective ground plane

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    A simple compact broadband circularly polarized monopole antenna, which comprises a simple monopole, a modified ground plane with an implementing triangular stub and two asymmetrically connected U-shaped parasitic strips, is proposed. Simulation results show that the proposed compact antenna (0.62λo×0.68λo) achieves a 10-dB impedance bandwidth (IBW) of 111% (1.7 to 5.95 GHz) and a 3-dB axial ratio bandwidth (ARBW) of 61% (3.3–6.2 GHz) with a peak gain between 2.9–4 dBi for the entire ARBW. With its broad IBW and ARBW, compact size and simple structure, the proposed antenna is suitable for different wireless communications

    High resolution dynamical mapping of social interactions with active RFID

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    In this paper we present an experimental framework to gather data on face-to-face social interactions between individuals, with a high spatial and temporal resolution. We use active Radio Frequency Identification (RFID) devices that assess contacts with one another by exchanging low-power radio packets. When individuals wear the beacons as a badge, a persistent radio contact between the RFID devices can be used as a proxy for a social interaction between individuals. We present the results of a pilot study recently performed during a conference, and a subsequent preliminary data analysis, that provides an assessment of our method and highlights its versatility and applicability in many areas concerned with human dynamics

    The Ecm11-Gmc2 complex promotes synaptonemal complex formation through assembly of transverse filaments in budding yeast

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    During meiosis, homologous chromosomes pair at close proximity to form the synaptonemal complex (SC). This association is mediated by transverse filament proteins that hold the axes of homologous chromosomes together along their entire length. Transverse filament proteins are highly aggregative and can form an aberrant aggregate called the polycomplex that is unassociated with chromosomes. Here, we show that the Ecm11-Gmc2 complex is a novel SC component, functioning to facilitate assembly of the yeast transverse filament protein, Zip1. Ecm11 and Gmc2 initially localize to the synapsis initiation sites, then throughout the synapsed regions of paired homologous chromosomes. The absence of either Ecm11 or Gmc2 substantially compromises the chromosomal assembly of Zip1 as well as polycomplex formation, indicating that the complex is required for extensive Zip1 polymerization. We also show that Ecm11 is SUMOylated in a Gmc2-dependent manner. Remarkably, in the unSUMOylatable ecm11 mutant, assembly of chromosomal Zip1 remained compromised while polycomplex formation became frequent. We propose that the Ecm11-Gmc2 complex facilitates the assembly of Zip1 and that SUMOylation of Ecm11 is critical for ensuring chromosomal assembly of Zip1, thus suppressing polycomplex formation

    Budding yeast ATM/ATR control meiotic double-strand break (DSB) levels by down-regulating Rec114, an essential component of the DSB-machinery

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    An essential feature of meiosis is Spo11 catalysis of programmed DNA double strand breaks (DSBs). Evidence suggests that the number of DSBs generated per meiosis is genetically determined and that this ability to maintain a pre-determined DSB level, or "DSB homeostasis", might be a property of the meiotic program. Here, we present direct evidence that Rec114, an evolutionarily conserved essential component of the meiotic DSB-machinery, interacts with DSB hotspot DNA, and that Tel1 and Mec1, the budding yeast ATM and ATR, respectively, down-regulate Rec114 upon meiotic DSB formation through phosphorylation. Mimicking constitutive phosphorylation reduces the interaction between Rec114 and DSB hotspot DNA, resulting in a reduction and/or delay in DSB formation. Conversely, a non-phosphorylatable rec114 allele confers a genome-wide increase in both DSB levels and in the interaction between Rec114 and the DSB hotspot DNA. These observations strongly suggest that Tel1 and/or Mec1 phosphorylation of Rec114 following Spo11 catalysis down-regulates DSB formation by limiting the interaction between Rec114 and DSB hotspots. We also present evidence that Ndt80, a meiosis specific transcription factor, contributes to Rec114 degradation, consistent with its requirement for complete cessation of DSB formation. Loss of Rec114 foci from chromatin is associated with homolog synapsis but independent of Ndt80 or Tel1/Mec1 phosphorylation. Taken together, we present evidence for three independent ways of regulating Rec114 activity, which likely contribute to meiotic DSBs-homeostasis in maintaining genetically determined levels of breaks

    GAPS-megacities: A new global platform for investigating persistent organic pollutants and chemicals of emerging concern in urban air

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    A pilot study was initiated in 2018 under the Global Atmospheric Passive Sampling (GAPS) Network named GAPS-Megacities. This study included 20 megacities/major cities across the globe with the goal of better understanding and comparing ambient air levels of persistent organic pollutants and other chemicals of emerging concern, to which humans residing in large cities are exposed. The first results from the initial period of sampling are reported for 19 cities for several classes of flame retardants (FRs) including organophosphate esters (OPEs), polybrominated diphenyl ethers (PBDEs), and halogenated flame retardants (HFRs) including new flame retardants (NFRs), tetrabromobisphenol A (TBBPA) and hexabromocyclododecane (HBCDD). The two cities, New York (USA) and London (UK) stood out with ∼3.5 to 30 times higher total FR concentrations as compared to other major cities, with total concentrations of OPEs of 15,100 and 14,100 pg/m, respectively. Atmospheric concentrations of OPEs significantly dominated the FR profile at all sites, with total concentrations in air that were 2–5 orders of magnitude higher compared to other targeted chemical classes. A moderately strong and significant correlation (r = 0.625, p < 0.001) was observed for Gross Domestic Product index of the cities with total OPEs levels. Although large differences in FR levels were observed between some cities, when averaged across the five United Nations regions, the FR classes were more evenly distributed and varied by less than a factor of five. Results for Toronto, which is a ‘reference city’ for this study, agreed well with a more in-depth investigation of the level of FRs over different seasons and across eight sites representing different urban source sectors (e.g. traffic, industrial, residential and background). Future sampling periods under this project will investigate trace metals and other contaminant classes, linkages to toxicology, non-targeted analysis, and eventually temporal trends. The study provides a unique urban platform for evaluating global exposome.A global study across 20 megacities/major cities reporting urban air concentrations of flame retardants and plasticizers.Authors thank the United Nations Environment Programme (UNEP) and the Chemicals Management Plan (CMP) for financial support. The worldwide implementation of the Global Monitoring Plan is made possible thanks to the generous contributions to the Stockholm Convention Voluntary Trust Fund from the Governments of Japan, Norway, Sweden, and through the European Commission’s Thematic Programme for Environment andSustainable Management of Natural Resources, including Energy (ENRTP). Further, the contribution of the projects to support POPs monitoring activities in regions, funded through the Global Environment Facility (GEF) and the Strategic Approach to International Chemicals Management (SAICM), is greatly acknowledged. Monitoring activities and data collection and analysis are implemented in the five UN regions in cooperation with strategic partners and through the involvement of Regional Organization Groups and Global Coordination Group. We also thank Yasuyuki Shibata and Yoshikatsu Takazawa (Tokyo, Japan); Juan Mu~noz-Arnanz (Madrid, Spain) and Dilek €Ozkan and Sinan Kızıltug (_Istanbul, Turkey) for their help and assistance in the sampling campaign
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