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381.
Identification of S6K2 as a centrosome-located kinase 总被引:1,自引:0,他引:1
Ribosomal S6 kinase 2 (S6K2) acts downstream of the mammalian target of rapamycin (mTOR). Here, we show that some S6K2 localize at the centrosome throughout the cell cycle. S6K2 is found in the pericentriolar area of the centrosome. S6K2 centrosomal localization is unaffected by serum withdrawal or treatment with rapamycin, wortmannin, U0126, or phorbol-12-myristate-13-acetate (PMA). Unlike S6K2, S6 kinase 1 (S6K1) does not localize at the centrosome, suggesting the two kinases may also have nonoverlapping functions. Our data suggest that centrosomal S6K2 may have a role in the phosphoinositide-3-kinase (PI3K)/Akt/mTOR signaling pathway that has also been detected in the centrosome. 相似文献
382.
Bcl-2 Expression and p38MAPK Activity in Cells Infected with Influenza A Virus: IMPACT ON VIRALLY INDUCED APOPTOSIS AND VIRAL REPLICATION* 总被引:1,自引:0,他引:1
383.
384.
Caterina Romano Carratelli Nello Mazzola Rossella Paolillo Sabato Sorrentino & Antonietta Rizzo 《FEMS immunology and medical microbiology》2009,57(2):116-124
Monocytes are pivotal effector cells of the innate immune system that are vital for recognizing and eliminating invasive microbial pathogens. When microbial products bind to pathogen-recognition receptors, monocytes are activated and release a broad array of cytokines and defensins that orchestrate the host innate and adaptive immune responses. The aim of the present study is to investigate whether Toll-like receptor-4 (TLR4) mediates human β-defensin-2 (HBD-2) induction in response to Chlamydia pneumoniae in mononuclear cells. We showed that TLR4 is expressed in U937 cells and monocytes infected with viable microorganisms in a time-dependent fashion, while heat-inactivated microorganisms induced a lesser expression, albeit still significant, of TLR4 compared with viable organisms; flow cytometric analysis, in particular, revealed a higher level of TLR4 expression at 48 and 72 h postinfection. In addition, U937 cells and monocytes responded to C. pneumoniae in a TLR4-dependent manner with induction of mRNA and protein of the antimicrobial peptide HBD-2. The treatment of cells with TLR4-neutralizing antibody resulted in a decrease in C. pneumoniae- induced HBD-2 production. This study reveals that TLRs not only recognize ligands but also the types of effector molecules induced, namely, antimicrobial peptides. An understanding of the importance of the TLR-mediated antimicrobial mechanisms may provide new avenues for the development of therapeutic regimens aimed at activating the body's own defenses by stimulating TLR-dependent pathways. 相似文献
385.
386.
Galbusera F Bertolazzi L Balossino R Dubini G 《Biomechanics and modeling in mechanobiology》2009,8(3):209-216
This paper presents a numerical model of a porous, hydroxyapatite-based bone graft also suitable as a drug delivery device.
The graft was positioned in different sites and with different porosities inside a human femur model. The structural analyses
were carried out to verify the graft mechanical strength, using the Tsai–Wu criterion, and the maximum porosity at which static
failure does not occur. A local stress shielding risk was also calculated as the ratio between the bone stress in the intact
condition and the stress after implantation of the graft. Drug release kinetics was calculated by means of the finite element
method. High porosity grafts were found to fail in all implantation sites. Lower porosity grafts showed to have adequate strength
if implanted in some positions, while provided insufficient resistance for other implantation sites. Drug release kinetics
was found to be strongly dependent both on the porosity of the graft and the bone density near the bone-graft interface. 相似文献
387.
Raffaella Melzi Barbara Antonioli Alessia Mercalli Manuela Battaglia Andrea Valle Stefano Pluchino Rossella Galli Valeria Sordi Emanuele Bosi Gianvito Martino Ezio Bonifacio Claudio Doglioni Lorenzo Piemonti 《PloS one》2010,5(4)
Background
Data available on the immunomodulatory properties of neural stem/precursor cells (NPC) support their possible use as modulators for immune-mediated process. The aim of this study was to define whether NPC administered in combination with pancreatic islets prevents rejection in a fully mismatched allograft model.Methodology/Principal Finding
Diabetic Balb/c mice were co-transplanted under the kidney capsule with pancreatic islets and GFP+ NPC from fully mismatched C57BL/6 mice. The following 4 groups of recipients were used: mice receiving islets alone; mice receiving islets alone and treated with standard immunosuppression (IL-2Rα chain mAbs + FK506 + Rapamycin); mice receiving a mixed islet/NPC graft under the same kidney capsule (Co-NPC-Tx); mice receiving the islet graft under the left kidney capsule and the NPC graft under the right kidney capsule (NPC-Tx). Our results demonstrate that only the co-transplantation and co-localization of NPC and islets (Co-NPC-Tx) induce stable long-term graft function in the absence of immunosuppression. This condition is associated with an expansion of CD4+CD25+FoxP3+ T regulatory cells in the spleen. Unfortunately, stable graft function was accompanied by constant and reproducible development of NPC-derived cancer mainly sustained by insulin secretion.Conclusion
These data demonstrate that the use of NPC in combination with islets prevents graft rejection in a fully mismatched model. However, the development of NPC-derived cancer raises serious doubts about the safety of using adult stem cells in combination with insulin-producing cells outside the original microenvironment. 相似文献388.
389.
390.
G. Simoni B. Brambati C. Danesino G. L. Terzoli L. Romitti F. Rossella M. Fraccaro 《Human genetics》1984,66(2-3):252-259
Summary The results of the diagnostic application of first trimester trophoblast sampling in 100 pregnancies are reported in detail. Further improvement of the method for routine, direct chromosome analysis resulted in a technique which proved to be fast, simple, and efficient. We found that short-term incubation of villi permits the application of many experimental methods, such as visualization of sister chromatid exchanges and bromodeoxyuridine (BrdU) incorporation. Fetal karyotyping was successful in each of the 96 pregnancies in which fetal material was obtained from a total of 98 fetuses. There were 42 males and 56 females, and an abnormal chromosome constitution was found in 12 cases. Two trisomic fetuses were found among the eight pregnancies at risk for Duchenne muscular dystrophy, and this indicates that fetal sexing (which is achieved with our method in two hours) should not be performed without chromosome visualization. The results indicate a risk of 8% of an abnormal fetus for mothers aged 35 years or more, while the risk of failure of sampling and of spontaneous abortion after villi sampling were 4 and 6%, respectively. Enzyme determinations were performed in three pregnancies at risk for gangliosidosis GM1, Niemann-Pick disease, and Hurler syndrome. In this last case inconsistency between the results of the assay of iduronidase on chorionic villi and amniotic fluid cells was found. This unexplained error indicates the need for extensive characterisation in chorionic villi of the series of enzymes involved in metabolic diseases. 相似文献