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11.
Gwendlyn Kollmorgen Birgit Bossenmaier Gerhard Niederfellner Hans-Ulrich H?ring Reiner Lammers 《PloS one》2012,7(12)
Cub domain containing protein 1 (CDCP1) is strongly expressed in tumors derived from lung, colon, ovary, or kidney. It is a membrane protein that is phosphorylated and then bound by Src family kinases. Although expression and phosphorylation of CDCP1 have been investigated in many tumor cell lines, the CDCP1 features responsible for transformation have not been fully evaluated. This is in part due to the lack of an experimental system in which cellular transformation depends on expression of exogenous CDCP1 and Src. Here we use retrovirus mediated co-overexpression of c-Src and CDCP1 to induce focus formation of NIH3T3 cells. Employing different mutants of CDCP1 we show that for a full transformation capacity, the intact amino- and carboxy-termini of CDCP1 are essential. Mutation of any of the core intracellular tyrosine residues (Y734, Y743, or Y762) abolished transformation, and mutation of a palmitoylation motif (C689,690G) strongly reduced it. Src kinase binding to CDCP1 was not required since Src with a defective SH2 domain generated even more CDCP1 dependent foci whereas Src myristoylation was necessary. Taken together, the focus formation assay allowed us to define structural requirements of CDCP1/Src dependent transformation and to characterize the interaction of CDCP1 and Src. 相似文献
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13.
Sven Pischke Anett Gisa Pothakamuri Venkata Suneetha Steffen Bj?rn Wiegand Richard Taubert Jerome Schlue Karsten Wursthorn Heike Bantel Regina Raupach Birgit Bremer Behrend Johann Zacher Reinhold Ernst Schmidt Michael Peter Manns Kinan Rifai Torsten Witte Heiner Wedemeyer 《PloS one》2014,9(1)
Background
Hepatitis E virus (HEV) infection takes a clinically silent, self-limited course in the far majority of cases. Chronic hepatitis E has been reported in some cohorts of immunocompromised individuals. The role of HEV infections in patients with autoimmune hepatitis (AIH) is unknown.Methods
969 individuals were tested for anti-HEV antibodies (MP-diagnostics) including 208 patients with AIH, 537 healthy controls, 114 patients with another autoimmune disease, rheumatoid arthritis (RA), and 109 patients with chronic HCV- or HBV-infection (HBV/HCV). Patients with AIH, RA and HBV/HCV were tested for HEV RNA. HEV-specific proliferative T cell responses were investigated using CFSE staining and in vitro stimulation of PBMC with overlapping HEV peptides.Results
HEV-antibodies tested more frequently positive in patients with AIH (n = 16; 7.7%) than in healthy controls (n = 11; 2.0%; p = 0.0002), patients with RA (n = 4; 3.5%; p = 0.13) or patients with HBV/HCV infection (n = 2; 2.8%; p = 0.03). HEV-specific T cell responses could be detected in all anti-HEV-positive AIH patients. One AIH patient receiving immunosuppression with cyclosporin and prednisolone and elevated ALT levels had acute hepatitis E but HEV viremia resolved after reducing immunosuppressive medication. None of the RA or HBV/HCV patients tested HEV RNA positive.Conclusions
Patients with autoimmune hepatitis but not RA or HBV/HCV patients are more likely to test anti-HEV positive. HEV infection should been ruled out before the diagnosis of AIH is made. Testing for HEV RNA is also recommended in AIH patients not responding to immunosuppressive therapy. 相似文献14.
Dorthe Aasland Birgit Oppmann Joachim Gr?tzinger Stefan Rose-John Karl-Josef Kallen 《Journal of molecular biology》2002,315(4):637-646
To elucidate the function of the two cytokine-binding modules (CBM) of the leukemia inhibitory factor receptor (LIFR), receptor chimeras of LIFR and the interleukin-6 receptor (IL-6R) were constructed. Either the NH(2)-terminal (chimera RILLIFdeltaI) or the COOH-terminal LIFR CBM (chimera RILLIFdeltaII) were replaced by the structurally related CBM of the IL-6R which does not bind LIF. Chimera RILLIFdeltaI is functionally inactive, whereas RILLIFdeltaII binds LIF and mediates signalling as efficiently as the wild-type LIFR. Deletion mutants of the LIFR revealed that both the NH(2)-terminal CBM and the Ig-like domain of the LIFR are involved in LIF binding, presumably via the LIF site III epitope. The main function of the COOH-terminal CBM of the LIFR is to position the NH(2)-terminal CBM and the Ig-like domain, so that these can bind to LIF. In analogy to a recently published model of the IL-6R complex, a model of the active LIFR complex is suggested which positions the COOH-terminal CBM at LIF site I and the NH(2)-terminal CBM and the Ig-like domain at site III. An additional contact is postulated between the Ig-like domain of gp130 and the NH(2)-terminal CBM of the LIFR. 相似文献
15.
Frank Jauker Birgit Bondarenko Heiko C. Becker Ingolf Steffan‐Dewenter 《Agricultural and Forest Entomology》2012,14(1):81-87
- 1 Declining numbers in honeybees and various wild bee species pose a threat to global pollination services. The identification and quantification of the pollination service provided by different taxa within the pollinator guild is a prerequisite for the successful establishment of nature conservation and crop management regimes.
- 2 Wild bees and hoverflies are considered to be valuable pollinators in agricultural and natural systems. Although some information on pollination efficiency of individual pollinator species is available, comparative studies of both taxa at different densities are rare. In the present study, the efficiency of the solitary mason bee Osmia rufa and two hoverfly species (Eristalis tenax and Episyrphus balteatus) as pollinators of oilseed rape Brassica napus was examined in a standardized caged plant breeding regime. Honeybee Apis mellifera colonies were used as a reference pollinator taxon.
- 3 Yield parameters responded differently to pollinator density and identity. Fruit set and number of seeds per pod increased with increasing pollinator density, although these were stronger in the mason bee than the hoverfly treatment. Weight per 1000 seeds did not respond to any pollinator treatment, indicating that seed quality was not affected. Oilseed rape yield in the highest tested densities of both pollinator taxa resulted in yield values close to the efficiency of small honeybee colonies.
- 4 Hoverflies required approximately five‐fold densities of the red mason bees to reach a similar fruit set and yield. Thus, mason bees are more efficient in plant breeding and managed pollination systems. Both natural pollinator taxa, however, are of potential value in open and closed crop production systems.
16.
Martina Inga Kirsch Birgit Hülseweh Christoph Nacke Torsten Rülker Thomas Schirrmann Hans-Jürgen Marschall Michael Hust Stefan Dübel 《BMC biotechnology》2008,8(1):66
Background
Venezuelan equine encephalitis virus (VEEV) belongs to the Alphavirus group. Several species of this family are also pathogenic to humans and are recognized as potential agents of biological warfare and terrorism. The objective of this work was the generation of recombinant antibodies for the detection of VEEV after a potential bioterrorism assault or an natural outbreak of VEEV. 相似文献17.
RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain 总被引:21,自引:0,他引:21
Deane R Du Yan S Submamaryan RK LaRue B Jovanovic S Hogg E Welch D Manness L Lin C Yu J Zhu H Ghiso J Frangione B Stern A Schmidt AM Armstrong DL Arnold B Liliensiek B Nawroth P Hofman F Kindy M Stern D Zlokovic B 《Nature medicine》2003,9(7):907-913
Amyloid-beta peptide (Abeta) interacts with the vasculature to influence Abeta levels in the brain and cerebral blood flow, providing a means of amplifying the Abeta-induced cellular stress underlying neuronal dysfunction and dementia. Systemic Abeta infusion and studies in genetically manipulated mice show that Abeta interaction with receptor for advanced glycation end products (RAGE)-bearing cells in the vessel wall results in transport of Abeta across the blood-brain barrier (BBB) and expression of proinflammatory cytokines and endothelin-1 (ET-1), the latter mediating Abeta-induced vasoconstriction. Inhibition of RAGE-ligand interaction suppresses accumulation of Abeta in brain parenchyma in a mouse transgenic model. These findings suggest that vascular RAGE is a target for inhibiting pathogenic consequences of Abeta-vascular interactions, including development of cerebral amyloidosis. 相似文献
18.
Hansen JB Westergaard M Thrue CA Giwercman B Oerum H 《Nucleosides, nucleotides & nucleic acids》2003,22(5-8):1607-1609
Full-length and 4 nucleotides truncated Locked Nucleic Acid (LNA) modifications of ISIS 3521 were compared for antisense properties in a cellular assay. ISIS 3521 is a 20-mer phosphorothioate designed to hybridise to human protein kinase C-alpha (PKC-alpha) mRNA and is currently submitted to clinical trials against cancer. We report that LNA can potentate this antisense oligo and retain the antisense potential with shorter oligos. 相似文献
19.
20.
Stephen Mosher Heike Seybold Patricia Rodriguez Mark Stahl Kelli A. Davies Sajeewani Dayaratne Santiago A. Morillo Michael Wierzba Bruno Favery Harald Keller Frans E. Tax Birgit Kemmerling 《The Plant journal : for cell and molecular biology》2013,73(3):469-482
The tyrosine‐sulfated peptides PSKα and PSY1 bind to specific leucine‐rich repeat surface receptor kinases and control cell proliferation in plants. In a reverse genetic screen, we identified the phytosulfokine (PSK) receptor PSKR1 as an important component of plant defense. Multiple independent loss‐of‐function mutants in PSKR1 are more resistant to biotrophic bacteria, show enhanced pathogen‐associated molecular pattern responses and less lesion formation after infection with the bacterial pathogen Pseudomonas syringae pv. tomato DC3000. By contrast, pskr1 mutants are more susceptible to necrotrophic fungal infection with Alternaria brassicicola, show more lesion formation and fungal growth which is not observed on wild‐type plants. The antagonistic effect on biotrophic and necrotrophic pathogen resistance is reflected by enhanced salicylate and reduced jasmonate responses in the mutants, suggesting that PSKR1 suppresses salicylate‐dependent defense responses. Detailed analysis of single and multiple mutations in the three paralogous genes PSKR1, ‐2 and PSY1‐receptor (PSY1R) determined that PSKR1 and PSY1R, but not PSKR2, have a partially redundant effect on plant immunity. In animals and plants, peptide sulfation is catalyzed by a tyrosylprotein sulfotransferase (TPST). Mutants lacking TPST show increased resistance to bacterial infection and increased susceptibility to fungal infection, mimicking the triple receptor mutant phenotypes. Feeding experiments with PSKα in tpst‐1 mutants partially restore the defense‐related phenotypes, indicating that perception of the PSKα peptide has a direct effect on plant defense. These results suggest that the PSKR subfamily integrates growth‐promoting and defense signals mediated by sulfated peptides and modulates cellular plasticity to allow flexible adjustment to environmental changes. 相似文献