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961.
Ranya Hassan Shinya Suzu Masateru Hiyoshi Naoko Takahashi-Makise Takamasa Ueno Tsutomu Agatsuma Hirofumi Akari Jun Komano Yutaka Takebe Kazuo Motoyoshi Seiji Okada 《Journal of cellular physiology》2009,221(2):458-468
HIV-1 Nef accelerates the progression to AIDS by binding with and activating a Src kinase Hck, but underlying molecular basis is not understood. We revealed that Nef disturbed N-glycosylation/trafficking of a cytokine receptor Fms in an Hck-dependent manner, a possible trigger to worsen uncontrolled immune system. Here, we provide direct evidence that dys-regulated activation of Hck pre-localized to the Golgi apparatus causes this Fms maturation arrest. A striking change in Hck induced by Nef other than activation was its skewed localization to the Golgi due to predominant Golgi-localization of Nef. Studies with different Nef alleles and their mutants showed a clear correlation among higher Nef-Hck affinity, stronger Hck activation, severe Golgi-localization of Hck and severe Fms maturation arrest. Studies with a newly discovered Nef-Hck binding blocker 2c more clearly showed that skewed Golgi-localization of active Hck was indeed the cause of Fms maturation arrest. 2c blocked Nef-induced skewed Golgi-localization of an active form of Hck (Hck-P2A) and Fms maturation arrest by Nef/Hck-P2A, but showed no inhibition on Hck-P2A kinase activity. Our finding establishes an intriguing link between the pathogenesis of Nef and a newly emerging concept that the Golgi-localized Src kinases regulate the Golgi function. J. Cell. Physiol. 221: 458–468, 2009. © 2009 Wiley-Liss, Inc. 相似文献
962.
Amanda Giamberardino Mahmoud Labib Eman M. Hassan Jason A. Tetro Susan Springthorpe Syed A. Sattar Maxim V. Berezovski Maria C. DeRosa 《PloS one》2013,8(11)
DNA aptamers were developed against murine norovirus (MNV) using SELEX (Systematic Evolution of Ligands by EXponential enrichment). Nine rounds of SELEX led to the discovery of AG3, a promising aptamer with very high affinity for MNV as well as for lab-synthesized capsids of a common human norovirus (HuNoV) outbreak strain (GII.3). Using fluorescence anisotropy, AG3 was found to bind with MNV with affinity in the low picomolar range. The aptamer could cross-react with HuNoV though it was selected against MNV. As compared to a non-specific DNA control sequence, the norovirus-binding affinity of AG3 was about a million-fold higher. In further tests, the aptamer also showed nearly a million-fold higher affinity for the noroviruses than for the feline calicivirus (FCV), a virus similar in size and structure to noroviruses. AG3 was incorporated into a simple electrochemical sensor using a gold nanoparticle-modified screen-printed carbon electrode (GNPs-SPCE). The aptasensor could detect MNV with a limit of detection of approximately 180 virus particles, for possible on-site applications. The lead aptamer candidate and the aptasensor platform show promise for the rapid detection and identification of noroviruses in environmental and clinical samples. 相似文献
963.
David Gothard Emma L. Smith Janos M. Kanczler Cameron R. Black Julia A. Wells Carol A. Roberts Lisa J. White Omar Qutachi Heather Peto Hassan Rashidi Luis Rojo Molly M. Stevens Alicia J. El Haj Felicity R. A. J. Rose Kevin M. Shakesheff Richard O. C. Oreffo 《PloS one》2015,10(12)
The current study has investigated the use of decellularised, demineralised bone extracellular matrix (ECM) hydrogel constructs for in vivo tissue mineralisation and bone formation. Stro-1-enriched human bone marrow stromal cells were incorporated together with select growth factors including VEGF, TGF-β3, BMP-2, PTHrP and VitD3, to augment bone formation, and mixed with alginate for structural support. Growth factors were delivered through fast (non-osteogenic factors) and slow (osteogenic factors) release PLGA microparticles. Constructs of 5 mm length were implanted in vivo for 28 days within mice. Dense tissue assessed by micro-CT correlated with histologically assessed mineralised bone formation in all constructs. Exogenous growth factor addition did not enhance bone formation further compared to alginate/bone ECM (ALG/ECM) hydrogels alone. UV irradiation reduced bone formation through degradation of intrinsic growth factors within the bone ECM component and possibly also ECM cross-linking. BMP-2 and VitD3 rescued osteogenic induction. ALG/ECM hydrogels appeared highly osteoinductive and delivery of angiogenic or chondrogenic growth factors led to altered bone formation. All constructs demonstrated extensive host tissue invasion and vascularisation aiding integration and implant longevity. The proposed hydrogel system functioned without the need for growth factor incorporation or an exogenous inducible cell source. Optimal growth factor concentrations and spatiotemporal release profiles require further assessment, as the bone ECM component may suffer batch variability between donor materials. In summary, ALG/ECM hydrogels provide a versatile biomaterial scaffold for utilisation within regenerative medicine which may be tailored, ultimately, to form the tissue of choice through incorporation of select growth factors. 相似文献
964.
Elizabeth Scribner Olivier Saut Paula Province Asim Bag Thierry Colin Hassan M. Fathallah-Shaykh 《PloS one》2014,9(12)
Glioblastoma multiforme (GBM) causes significant neurological morbidity and short survival times. Brain invasion by GBM is associated with poor prognosis. Recent clinical trials of bevacizumab in newly-diagnosed GBM found no beneficial effects on overall survival times; however, the baseline health-related quality of life and performance status were maintained longer in the bevacizumab group and the glucocorticoid requirement was lower. Here, we construct a clinical-scale model of GBM whose predictions uncover a new pattern of recurrence in 11/70 bevacizumab-treated patients. The findings support an exception to the Folkman hypothesis: GBM grows in the absence of angiogenesis by a cycle of proliferation and brain invasion that expands necrosis. Furthermore, necrosis is positively correlated with brain invasion in 26 newly-diagnosed GBM. The unintuitive results explain the unusual clinical effects of bevacizumab and suggest new hypotheses on the dynamic clinical effects of migration by active transport, a mechanism of hypoxia-driven brain invasion. 相似文献
965.
Background
Oedema, commonly known as tissue swelling, occurs mainly on the leg and the arm. The condition may be associated with a range of causes such as venous diseases, trauma, infection, joint disease and orthopaedic surgery. Oedema is caused by both lymphatic and chronic venous insufficiency, which leads to pooling of blood and fluid in the extremities. This results in swelling, mild redness and scaling of the skin, all of which can culminate in ulceration. 相似文献966.
Prosaposin (SGP-1) and GM2 activator protein (GM2AP) are soluble sphingolipid activator proteins (SAPs) that are targeted to the lysosomal compartment of Sertoli cells to aid hydrolases in the breakdown of glycosphingolipids. To reach the lysosome, most soluble proteins must interact with the mannose 6-phosphate receptor (MPR). To be sorted from the Golgi, the MPR must bind to the Golgi associated, gamma-adaptin homologous, ARF binding proteins (GGAs), a group of monomeric adaptor proteins responsible for the recruitment of clathrin. It is well established, however, that the lysosomes of I-cell disease (ICD) patients have near normal levels of several lysosomal proteins, including prosaposin and GM2AP. ICD results from a mutation in the phosphotransferase that adds mannose 6-phosphate to hydrolases. Thus, prosaposin and GM2AP can traffic to lysosomes in a MPR independent manner. Previous work has demonstrated that an interaction with sphingomyelin in the Golgi membrane is necessary for the targeting of prosaposin by an unknown receptor. Using a TM4 Sertoli cell line, we tested the hypothesis that prosaposin and GM2AP are targeted to the lysosomal compartment via the sortilin receptor, which has been recently shown to have a GGA binding motif. Interestingly, dominant-negative GGAs, unable to bind clathrin to shuttle from the Golgi, prevented the trafficking of prosaposin and GM2AP to lysosomes. A dominant negative construct of sortilin lacking the GGA binding domain retained prosaposin and GM2AP in the Golgi. In conclusion, our results showed that the trafficking of prosaposin and GM2AP to the lysosome is dependent on sortilin. 相似文献
967.
The effects of azadirachtin/Neemazal on adults, emergence, and life table parameters of Trichogramma cacoeciae Marchal were studied. The adults were exposed to fresh residues of the insecticide applied on glass plates. Based on the dose-response study, the LC50 value was 1330 ppm or 13.3 microg (AI)/ml. The effect of Neemazal on three developmental stages of the parasitoid was tested by dipping parasitized Sitotroga cerealella (Olivier) and Cydia pomonella (L.) eggs at the field-recommended concentration 3, 6, and 9 d after parasitization corresponding to larval, prepupal, and pupal stages. The emergence of adult parasitoids was adversely affected in both hosts, but the adverse effect was more in S. cerealella eggs compared with C. pomonella. The adult emergence was reduced by 73.3 and 33.76% in Sitotroga and Cydia eggs compared with controls, respectively. Longevity and progeny production of the emergent adults did not differ significantly from control. Neemazal affected stable population parameters (r(m), T, and DT) significantly. The intrinsic rate of increase for the control and Neemazal-exposed populations was 0.340 and 0.335 female offspring per female per day, respectively. Because some of postemergence life table parameters of adults were significantly reduced by the insecticide treatment, emergence rate of the parasitoid from treated eggs is not an adequate measure of ecological selectivity, and field studies are needed to determine the actual impact of neem on T. cacoeciae. 相似文献
968.
969.
970.
Mathematical algorithm for discovering states of expression from direct genetic comparison by microarrays 总被引:1,自引:0,他引:1
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Highly specific direct genome-scale expression discovery from two biological samples facilitates functional discovery of molecular systems. Here, expression data from cDNA arrays are ranked and curve-fitted. The algorithm uses filters based on the derivatives (slopes) of the curve fits. The rules are set to (i) filter the largest number of artifactual ratios from same-to-same datasets and (ii) maximize discovery from direct comparisons of different samples. The unsupervised discovery is optimized without lowering specificity. The false discovery rates are significantly lower than other methods. The discovered states of genetic expression facilitate functional discovery and are validated by real-time RT–PCR. Better quality improves sensitivity. 相似文献