149 research outputs found

    A bovine lymphosarcoma cell line infected with theileria annulata exhibits an irreversible reconfiguration of host cell gene expression

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    Theileria annulata, an intracellular parasite of bovine lymphoid cells, induces substantial phenotypic alterations to its host cell including continuous proliferation, cytoskeletal changes and resistance to apoptosis. While parasite induced modulation of host cell signal transduction pathways and NFκB activation are established, there remains considerable speculation on the complexities of the parasite directed control mechanisms that govern these radical changes to the host cell. Our objectives in this study were to provide a comprehensive analysis of the global changes to host cell gene expression with emphasis on those that result from direct intervention by the parasite. By using comparative microarray analysis of an uninfected bovine cell line and its Theileria infected counterpart, in conjunction with use of the specific parasitacidal agent, buparvaquone, we have identified a large number of host cell gene expression changes that result from parasite infection. Our results indicate that the viable parasite can irreversibly modify the transformed phenotype of a bovine cell line. Fifty percent of genes with altered expression failed to show a reversible response to parasite death, a possible contributing factor to initiation of host cell apoptosis. The genes that did show an early predicted response to loss of parasite viability highlighted a sub-group of genes that are likely to be under direct control by parasite infection. Network and pathway analysis demonstrated that this sub-group is significantly enriched for genes involved in regulation of chromatin modification and gene expression. The results provide evidence that the Theileria parasite has the regulatory capacity to generate widespread change to host cell gene expression in a complex and largely irreversible manner

    Dengue-1 Envelope Protein Domain III along with PELC and CpG Oligodeoxynucleotides Synergistically Enhances Immune Responses

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    The major weaknesses of subunit vaccines are their low immunogenicity and poor efficacy. Adjuvants can help to overcome some of these inherent defects with subunit vaccines. Here, we evaluated the efficacy of the newly developed water-in-oil-in-water multiphase emulsion system, termed PELC, in potentiating the protective capacity of dengue-1 envelope protein domain III. Unlike aluminum phosphate, dengue-1 envelope protein domain III formulated with PELC plus CpG oligodeoxynucleotides induced neutralizing antibodies against dengue-1 virus and increased the splenocyte secretion of IFN-γ after in vitro re-stimulation. The induced antibodies contained both the IgG1 and IgG2a subclasses. A rapid anamnestic neutralizing antibody response against a live dengue virus challenge was elicited at week 26 after the first immunization. These results demonstrate that PELC plus CpG oligodeoxynucleotides broaden the dengue-1 envelope protein domain III-specific immune responses. PELC plus CpG oligodeoxynucleotides is a promising adjuvant for recombinant protein based vaccination against dengue virus

    Berberine chloride can ameliorate the spatial memory impairment and increase the expression of interleukin-1beta and inducible nitric oxide synthase in the rat model of Alzheimer's disease

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    BACKGROUND: Berberine is the major alkaloidal component of Rhizoma coptidis, and has multiple pharmacological effects including inhibiting acetylcholinesterase, reducing cholesterol and glucose, lowering mortality in patients with chronic congestive heart failure and anti-inflammation etc. Thus berberine is a promising drug for diabetes, hyperlipemia, coronary artery disease and ischemic stroke etc. The present study was carried out to investigate the effect of berberine chloride on the spatial memory, inflammation factors interleukin-1 beta (IL-1beta) and inducible nitric oxide synthase (iNOS) expression in the rat model of Alzheimer's disease (AD) which was established by injecting Abeta (1–40) (5 microgram) into the rats hippocampuses bilaterally. RESULTS: The rats were given berberine chloride (50 mg/kg) by intragastric administration once daily for 14 days. The spatial memory was assayed by Morris water maze test, IL-1beta and iNOS in the hippocampus were assayed by immunohistochemistry and real time polymerase chain reaction (PCR). Intragastric administration of berberine significantly ameliorated the spatial memory impairment and increased the expression of IL-1beta, iNOS in the rat model of AD. CONCLUSION: Berberine might be beneficial to AD by intragastric administration though it might exaggerate the inflammation reaction

    Decrease in the production of beta-amyloid by berberine inhibition of the expression of beta-secretase in HEK293 cells

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    <p>Abstract</p> <p>Background</p> <p>Berberine (BER), the major alkaloidal component of <it>Rhizoma coptidis</it>, has multiple pharmacological effects including inhibition of acetylcholinesterase, reduction of cholesterol and glucose levels, anti-inflammatory, neuroprotective and neurotrophic effects. It has also been demonstrated that BER can reduce the production of beta-amyloid<sub>40/42</sub>, which plays a critical and primary role in the pathogenesis of Alzheimer's disease. However, the mechanism by which it accomplishes this remains unclear.</p> <p>Results</p> <p>Here, we report that BER could not only significantly decrease the production of beta-amyloid<sub>40/42 </sub>and the expression of beta-secretase (BACE), but was also able to activate the extracellular signal-regulated kinase1/2 (ERK1/2) pathway in a dose- and time-dependent manner in HEK293 cells stably transfected with APP695 containing the Swedish mutation. We also find that U0126, an antagonist of the ERK1/2 pathway, could abolish (1) the activation activity of BER on the ERK1/2 pathway and (2) the inhibition activity of BER on the production of beta-amyloid<sub>40/42 </sub>and the expression of BACE.</p> <p>Conclusion</p> <p>Our data indicate that BER decreases the production of beta-amyloid<sub>40/42 </sub>by inhibiting the expression of BACE via activation of the ERK1/2 pathway.</p

    A new inner tracker based on GEM detectors for the BES III experiment

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    A new inner tracker based on a cylindrical gas electron-multiplier detector is under development to replace the current inner drift chamber of the BES III spectrometer. The BES III experiment is carried out at the BEPC II e[Formula: see text]e[Formula: see text] collider in Beijing at center-of-mass energies in the tau-charm region with a design luminosity of 1.0 [Formula: see text] 10[Formula: see text] cm[Formula: see text]s[Formula: see text]. The new inner tracker consists of three cylindrical layers of triple GEM surrounding the interaction point, covering 93% of solid angle. To fulfill physics requirements, a spatial resolution of 130 μm must be achieved. Both planar and cylindrical prototypes have been built and tested. A custom ASIC using UMC 110-nm technology has been designed to provide charge and time measurements—the first prototype is in testing. Notable and innovative aspects of the new inner tracker and the performance of the detector prototypes and readout ASIC are reported here

    Performance of the micro-TPC Reconstruction for GEM Detectors at High Rate

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    Gas detectors are one of the pillars of the research in fundamental physics. Since many years, a new concept of detectors, the Micro Pattern Gas Detectors, allows to overcome many of the problems of other types of commonly used detectors, as drift chambers and microstrips, reducing the discharge rate and increasing the radiation tolerance. Among these, one of the most commonly used is the Gas Electron Multiplier. Commonly deployed as fast timing detectors and triggers, due to their fast response, high rate capability and high radiation hardness, they can also be used as trackers. The center of gravity readout technique allows to overcome the limit of the digital pads, whose spatial resolution is constrained by the pitch size. The presence of a high external magnetic field can distort the electronic cloud and affect the spatial resolution. The micro-TPC reconstruction method allows to reconstruct the three dimensional particle position as in a traditional Time Projection Chamber, but within a drift gap of a few millimeters. This method brings these detectors into a new perspective for what concerns the spatial resolution in strong magnetic field. In this report, the basis of this new technique will be shown and it will be compared to the traditional center of gravity. The results of a series of test beam performed with 10 x 10 cm2 planar prototypes in magnetic field will also be presented. This is one of the first implementations of this technique for GEM detectors in magnetic field and allows to reach unprecedented performance for gas detectors, up to a limit of 120 micron at 1T, one of the world's best results for MPGDs in strong magnetic field. The micro-TPC reconstruction has been recently tested at very high rates in a test beam at the MAMI facility; preliminary results of the test will be presented.Comment: Proceedings for "2017 IEEE Nuclear Science Symposium and Medical Imaging Conference (NSS/MIC)" (IEEE17) Conference, 21-28 October 2017, Atlanga, Georgia, USA (prepared for submission to IEEE Conference Record
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