564 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

    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

    EMPLOYMENT IN THE PRIVATE SECTOR IN OMAN: SECTOR-BASED APPROACH FOR LOCALIZATION

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    Purpose The objective of the study is to analyze the factors impeding Omanization policies in the selected sectors - Construction, Retail and Tourism of Oman economy and to find out the cause for the disparity created between the graduates and the jobs availability. Design/methodology/approach The study adopted both qualitative and quantitative analysis. The interview approach was administered to collect the data from the Government officials, employers of expats in the private sector,  Omani youth seeking employment and employees from Muscat, Sohar, and Salalah. Findings Lack of coordination between government and the private sector in the formulation of Omanization policies contributing to sustained high level expatriate workers in Oman’s private sector leaving a large gap between the Omani job seekers and job availability in the selected sectors. Practical Implications Every year, the number of graduates is exceeding the number of jobs available in the economy and this paper draws attention to align this alarming issue through proper suggestions. Social Implications There is an urgent need to improve the alignment between the qualification and skills bestowed on nationals by education systems and the needs of the market through devising proper mechanisms. Originality/value Very few studies have examined the harmony of Higher Education and market requirements in Oman. This is first hand study of its kind

    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

    THE TRANSITION TO A PG GRADING SYSTEM FOR ASPHALT CEMENT IN IRAQ

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    In Iraq, as well as many other developing countries the performance graded (PG) based System is not yet implemented to evaluate the currently used asphalt cernents for paving works. It appears that not only the unavailability of test equipments is resulting in this delay but also the lack of clear understanding of what steps could be taken to incorporate this system. This research is an attempt to highlight the important aspects of a (PG) system that can be readily implemented without the need for expensive equipments. It includes the development of a Performance based System employing the conventional test methods and available nomographs from literature. It also, shows how climatic data, traffic data, and asphalt binder properties can be combined to propose a possible major improvement for the specifications of asphalts in Iraq. To achieve the objective of this research, an extensive air temperature data for a period of 18 years was reviewed for five cities (Mosul. Kirkuk. Rutba, Baghdad, and Basrah) to establish the required PG asphalt binder for each city. Also, the currently used asphalt cements with penetration grades (40-50) and (60-70) were tested by both of conventional test methods and Superpave methods to determine the equivalent performance grade for each type of the penetration graded asphalt and to evaluate the capability for these two types of asphalt cement to satisfy the required performance of pavement for each city, The results indicate that both the new proposed method and Superpave method give the same final performance grade. The asphalt with penetration grade 40-50 is equivalent to PG70-16 while that with penetration grade 60-70 is equivalent to PG64-16

    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

    Interplay of Mre11 Nuclease with Dna2 plus Sgs1 in Rad51-Dependent Recombinational Repair

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    The Mre11/Rad50/Xrs2 complex initiates IR repair by binding to the end of a double-strand break, resulting in 5′ to 3′ exonuclease degradation creating a single-stranded 3′ overhang competent for strand invasion into the unbroken chromosome. The nuclease(s) involved are not well understood. Mre11 encodes a nuclease, but it has 3′ to 5′, rather than 5′ to 3′ activity. Furthermore, mutations that inactivate only the nuclease activity of Mre11 but not its other repair functions, mre11-D56N and mre11-H125N, are resistant to IR. This suggests that another nuclease can catalyze 5′ to 3′ degradation. One candidate nuclease that has not been tested to date because it is encoded by an essential gene is the Dna2 helicase/nuclease. We recently reported the ability to suppress the lethality of a dna2Δ with a pif1Δ. The dna2Δ pif1Δ mutant is IR-resistant. We have determined that dna2Δ pif1Δ mre11-D56N and dna2Δ pif1Δ mre11-H125N strains are equally as sensitive to IR as mre11Δ strains, suggesting that in the absence of Dna2, Mre11 nuclease carries out repair. The dna2Δ pif1Δ mre11-D56N triple mutant is complemented by plasmids expressing Mre11, Dna2 or dna2K1080E, a mutant with defective helicase and functional nuclease, demonstrating that the nuclease of Dna2 compensates for the absence of Mre11 nuclease in IR repair, presumably in 5′ to 3′ degradation at DSB ends. We further show that sgs1Δ mre11-H125N, but not sgs1Δ, is very sensitive to IR, implicating the Sgs1 helicase in the Dna2-mediated pathway

    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

    Selective Inhibition of p300 HAT Blocks Cell Cycle Progression, Induces Cellular Senescence, and Inhibits the DNA Damage Response in Melanoma Cells

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    Epigenetic events, including covalent post-translational modifications of histones, have been demonstrated to have critical roles in tumor development and progression. The transcriptional coactivator p300/CBP possesses both histone acetyltransferase (HAT) activity and scaffolding properties that directly influence the transcriptional activation of targeted genes. We have used a potent and specific inhibitor of p300/CBP HAT activity, C646, in order to evaluate the functional contributions of p300/CBP HAT to tumor development and progression. Here we report that C646 inhibits the growth of human melanoma and other tumor cells and promotes cellular senescence. Global assessment of the p300 HAT transcriptome in human melanoma identified functional roles in promoting cell cycle progression, chromatin assembly, and activation of DNA repair pathways through direct transcriptional regulatory mechanisms. In addition, C646 is shown to promote sensitivity to DNA damaging agents, leading to the enhanced apoptosis of melanoma cells after combination treatment with cisplatin. Together, our data suggest that p300 HAT activity mediates critical growth regulatory pathways in tumor cells and may serve as a potential therapeutic target for melanoma and other malignancies by promoting cellular responses to DNA damaging agents that are currently ineffective against specific cancers
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