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| 2. |
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| 3. |
- Kazaks, A, et al.
(author)
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Stop codon insertion restores the particle formation ability of hepatitis B virus core-hantavirus nucleocapsid protein fusions
- 2002
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In: Intervirology. - : S. Karger AG. - 0300-5526 .- 1423-0100. ; 45:4-6, s. 340-349
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Journal article (peer-reviewed)abstract
- In recent years, epitopes of various origin have been inserted into the core protein of hepatitis B virus (HBc), allowing the formation of chimeric HBc particles. Although the C-terminus of a C-terminally truncated HBc (HBcΔ) tolerates the insertion of extended foreign sequences, the insertion capacity is still a limiting factor for the construction of multivalent vaccines. Previously, we described a new system to generate HBcΔ mosaic particles based on a read-through mechanism in an <i>Escherichia coli</i> suppressor strain [J Gen Virol 1997;78:2049–2053]. Those mosaic particles allowed the insertion of a 114-amino acid (aa)-long segment of a Puumala hantavirus (PUUV) nucleocapsid (N) protein. To study the value and the potential limitations of the mosaic approach in more detail, we investigated the assembly capacity of ‘non-mosaic’ HBcΔ fusion proteins and the corresponding mosaic constructs carrying 94, 213 and 433 aa of the hantaviral N protein. Whereas the fusion proteins carrying 94, 114, 213 or 433 aa were not assembled into HBcΔ particles, or only at a low yield, the insertion of a stop codon-bearing linker restored the ability to form particles with 94, 114 and 213 foreign aa. The mosaic particles formed exhibited PUUV-N protein antigenicity. Immunization of BALB/c mice with these mosaic particles carrying PUUV-N protein aa 1–114, aa 1–213 and aa 340–433, respectively, induced HBc-specific antibodies, whereas PUUV-N protein-specific antibodies were detected only in mice immunized with particles carrying N-terminal aa 1–114 or aa 1–213 of the N protein. Both the anti-HBc and anti-PUUV antibody responses were IgG1 dominated. In conclusion, stop codon suppression allows the formation of mosaic core particles carrying large-sized and ‘problematic’, e.g. hydrophobic, hantavirus sequences.
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| 7. |
- Nilsson, Jonas A, et al.
(author)
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Mnt loss triggers Myc transcription targets, proliferation, apoptosis, and transformation.
- 2004
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In: Mol Cell Biol. - 0270-7306. ; 24:4, s. 1560-9
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Journal article (peer-reviewed)abstract
- Myc oncoproteins are overexpressed in most cancers and are sufficient to accelerate cell proliferation and provoke transformation. However, in normal cells Myc also triggers apoptosis. All of the effects of Myc require its function as a transcription factor that dimerizes with Max. This complex induces genes containing CACGTG E-boxes, such as Ornithine decarboxylase (Odc), which harbors two of these elements. Here we report that in quiescent cells the Odc E-boxes are occupied by Max and Mnt, a putative Myc antagonist, and that this complex is displaced by Myc-Max complexes in proliferating cells. Knockdown of Mnt expression by stable retroviral RNA interference triggers many targets typical of the "Myc" response and provokes accelerated proliferation and apoptosis. Strikingly, these effects of Mnt knockdown are even manifest in cells lacking c-myc. Moreover, Mnt knockdown is sufficient to transform primary fibroblasts in conjunction with Ras. Therefore, Mnt behaves as a tumor suppressor. These findings support a model where Mnt represses Myc target genes and Myc functions as an oncogene by relieving Mnt-mediated repression.
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| 8. |
- Bashkanov, M., et al.
(author)
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Two-pion production in proton-proton collisions
- 2004
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In: Hadron Spectroscopy, Tenth International Conference on Hadron Spectrscopy, Aschaffenburg, Germany 31 August - 6 September 2003. - 0735401977 ; , s. 241-244
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Conference paper (other academic/artistic)
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| 9. |
- Beck, M., et al.
(author)
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A pulse-train laser driven XUV source for picosecond pump-probe experiments in the water window
- 2001
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In: Optics Communications. - 0030-4018 .- 1873-0310. ; 190:06-jan, s. 317-326
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Journal article (peer-reviewed)abstract
- We describe the development of a table top soft X-ray source based on a laser produced plasma. The plasma is produced by a Nd:YLF pulse-train laser which delivers pulse trains of up to 400 pulses each of about 25 ps duration, Number and energy of the micropulses are fully computer controlled adjustable for an optimum interaction with a rotating solid target. Spectral, spatial and temporal characteristics of the X-ray emission from Mylar and copper targets have been studied. A calibrated back-illuminated CCD camera together with a slit grating spectrograph were utilized for the measurement of the absolute soft X-ray photon fluxes. The temporal measurements were performed using a streak camera while the plasma size was measured with a zone plate. An application of the system in a X-ray absorption experiment is shown, The advantages of the system in view of possible optical pump and soft X-ray probe experiments will be discussed.
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| 10. |
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| 11. |
- Häussermann, Ulrich, et al.
(author)
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Alloys Bi1-xSbx under High-Pressure
- 2004
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In: Physical Review B. - 1098-0121. ; 69, s. 134203-1 - 134203-10
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Journal article (peer-reviewed)
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| 12. |
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| 13. |
- Kintscher, Ulrich, et al.
(author)
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PPARalpha inhibits TGF-beta-induced beta5 integrin transcription in vascular smooth muscle cells by interacting with Smad4
- 2002
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In: Circulation Research. - 0009-7330 .- 1524-4571. ; 91:11, s. e35-e44
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Journal article (peer-reviewed)abstract
- Integrins play an important role in vascular smooth muscle cell (VSMC) migration, a crucial event in the development of restenosis and atherosclerosis. Transforming growth factor-beta (TGF-beta) is highly expressed in restenotic and atherosclerotic lesions, and known to induce integrin expression. Peroxisome proliferator-activated receptor alpha (PPARalpha), a member of the nuclear receptor superfamily, regulates gene expression in a variety of vascular cells. We investigated the effects of PPARalpha ligands on TGF-beta-induced beta3 and beta5 integrin expression and potential interaction between PPARalpha and TGF-beta signaling. PPARalpha ligands WY-14643 (100 micromol/L) and 5,8,11,14-eicosatetranoic acid (ETYA, 50 micromol/L) inhibited TGF-beta-induced beta5 integrin protein expression by 72+/-6.8% and 73+/-7.1%, respectively (both P<0.05). TGF-beta-stimulated beta3 integrin expression was not affected by PPARalpha ligands. Both PPARalpha ligands also suppressed TGF-beta-induced beta5 integrin mRNA levels. PPARalpha ligands inhibited TGF-beta-inducible transcription of beta5 integrin by an interaction with a TGF-beta response element between nucleotides -63 and -44, which contains a Sp1/Sp3 transcription factor binding site. Nuclear complexes binding to the TGF-beta response region contained Sp1/Sp3 and TGF-beta-regulated Smad 2, 3, and 4 transcription factors. TGF-beta-stimulated Sp1/Smad4 nuclear complex formation was inhibited by WY-14643 and ETYA with a parallel induction of PPARalpha/Smad4 interactions. However, in vitro pull-down experiments failed to demonstrate direct binding between PPARalpha/Smad4. Both PPARalpha ligands blocked PDGF-directed migration of TGF-beta-pretreated VSMCs, a process mediated, in part, by beta5 integrins. The present study demonstrates that PPARalpha activators inhibit TGF-beta-induced beta5 integrin transcription in VSMCs through a novel indirect interaction between ligand-activated PPARalpha and the TGF-beta-regulated Smad4 transcription factors.
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| 14. |
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| 15. |
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| 16. |
- Korn, G., et al.
(author)
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Ultrashort 1-kHz laser plasma hard x-ray source
- 2002
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In: Optics Letters. - 0146-9592 .- 1539-4794. ; 27:10, s. 866-868
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Journal article (peer-reviewed)abstract
- We achieved a continuous, stable, ultrashort pulse hard x-ray point source by focusing 1.8-W, 1-kHz, 50-fs laser pulses onto a novel, 30-mum-diameter, high-velocity, liquid-metal gallium jet. This target geometry avoids most of the debris problems of solid targets and provides nearly 4pi illumination. Photon fluxes of 5 X 10(8) photons/s are generated in a two-component spectrum consisting of a broad continuum from 4 to 14 keV and strong K-alpha and K-beta emission lines at 9.25 and 10.26 keV. This source will find wide use in time-resolved x-ray diffraction studies and other applications.
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| 17. |
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| 18. |
- Kurisaki, Keiko, et al.
(author)
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Nuclear factor YY1 inhibits transforming growth factor beta- and bone morphogenetic protein-induced cell differentiation
- 2003
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In: Molecular and Cellular Biology. - 0270-7306 .- 1098-5549. ; 23:13, s. 4494-4510
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Journal article (peer-reviewed)abstract
- Smad proteins transduce transforming growth factor beta (TGF-beta) and bone morphogenetic protein (BMP) signals that regulate cell growth and differentiation. We have identified YY1, a transcription factor that positively or negatively regulates transcription of many genes, as a novel Smad-interacting protein. YY1 represses the induction of immediate-early genes to TGF-beta and BMP, such as the plasminogen activator inhibitor 1 gene (PAI-1) and the inhibitor of differentiation/inhibitor of DNA binding 1 gene (Id-1). YY1 inhibits binding of Smads to their cognate DNA elements in vitro and blocks Smad recruitment to the Smad-binding element-rich region of the PAI-1 promoter in vivo. YY1 interacts with the conserved N-terminal Mad homology 1 domain of Smad4 and to a lesser extent with Smad1, Smad2, and Smad3. The YY1 zinc finger domain mediates the association with Smads and is necessary for the repressive effect of YY1 on Smad transcriptional activity. Moreover, downregulation of endogenous YY1 by antisense and small interfering RNA strategies results in enhanced transcriptional responses to TGF-beta or BMP. Ectopic expression of YY1 inhibits, while knockdown of endogenous YY1 enhances, TGF-beta- and BMP-induced cell differentiation. In contrast, overexpression or knockdown of YY1 does not affect growth inhibition induced by TGF-beta or BMP. Accordingly, YY1 does not interfere with the regulation of immediate-early genes involved in the TGF-beta growth-inhibitory response, the cell cycle inhibitors p15 and p21, and the proto-oncogene c-myc. In conclusion, YY1 represses Smad transcriptional activities in a gene-specific manner and thus regulates cell differentiation induced by TGF-beta superfamily pathways.
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| 19. |
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| 20. |
- Möller, Christian, et al.
(author)
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Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-study)
- 2002
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In: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 109:2, s. 251-256
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Journal article (peer-reviewed)abstract
- Background: Children with allergic rhinitis are likely to develop asthma.Objective: The purpose of this investigation was to determine whether specific immunotherapy can prevent the development of asthma and reduce bronchial hyperresponsiveness in children with seasonal allergic rhinoconjunctivitis.Methods: From 6 pediatric allergy centers, 205 children aged 6 to 14 years (mean age, 10.7 years) with grass and/or birch pollen allergy but without any other clinically important allergy were randomized either to receive specific immunotherapy for 3 years or to an open control group. All subjects had moderate to severe hay fever symptoms, but at inclusion none reported asthma with need of daily treatment. Symptomatic treatment was limited to loratadine, levocabastine, sodium cromoglycate, and nasal budesonide. Asthma was evaluated clinically and by peak flow. Methacholine bronchial provocation tests were carried out during the season(s) and during the winter.Results: Before the start of immunotherapy, 20% of the children had mild asthma symptoms during the pollen season(s). Among those without asthma, the actively treated children had significantly fewer asthma symptoms after 3 years as evaluated by clinical diagnosis (odds ratio, 2.52; P < .05). Methacholine bronchial provocation test results improved significant in the active group (P < .05).Conclusion: Immunotherapy can reduce the development of asthma in children with seasonal rhinoconjunctivitis.
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| 21. |
- Nilsson, Jonas A, et al.
(author)
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Id2 is dispensable for myc-induced lymphomagenesis.
- 2004
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In: Cancer Res. - 0008-5472. ; 64:20, s. 7296-301
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Journal article (peer-reviewed)abstract
- The Emu-Myc transgenic mouse appears to be an accurate model of human Burkitt's lymphoma that bears MYC/Immunoglobulin gene translocations. Id2, a negative regulator of basic helix-loop-helix transcription factors, has also been proposed as a Myc target gene that drives the proliferative response of Myc by binding to and overriding the checkpoint functions of the retinoblastoma tumor suppressor protein. Targeted deletion of Id2 in mice results in defects in B-cell development and prevents the development of peripheral lymphoid nodes. In precancerous B cells and lymphomas that arise in Emu-Myc transgenic mice and in Burkitt's lymphomas, Id2 is overexpressed, suggesting that it plays a regulatory role in lymphoma development. Surprisingly, despite these connections, Emu-Myc mice lacking Id2 succumb to lethal B-cell lymphoma at rates comparable with wild-type Emu-Myc transgenics. Furthermore, precancerous splenic B cells lacking Id2 do not exhibit any significant defects in Myc-induced target gene transactivation and proliferation. However, due to their lack of secondary lymph nodes, Emu-Myc mice lacking Id2 rather succumb to disseminated lymphoma with an associated leukemia, with pronounced infiltrates of the bone marrow and other major organs. Collectively these findings argue that targeting Id2 functions may be ineffective in preventing Myc-associated malignancies.
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| 22. |
- Routh, Joyanto, 1968-, et al.
(author)
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Volatile organic acids and microbial processes in the Yegua formation, east-central Texas
- 2001
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In: Applied Geochemistry. - : Elsevier. - 0883-2927 .- 1872-9134. ; 16:2, s. 183-195
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Journal article (peer-reviewed)abstract
- Geochemical and microbiological evidence indicates that viable microorganisms produce and consume volatile organic acids (VOA) in the Yegua formation. Acetic and propionic acid concentrations in mudstones range from 200 to 1270 and 20 to 38 nmol·gdw−1 respectively, whereas concentrations in sands are 50–200 and less than 20 nmol·gdw−1. VOA concentrations in sediments and in laboratory incubations suggest net production of VOAs by microorganisms in mudstones, and net consumption of VOAs by SO4 reducing bacteria (SRB) in sands. Notably, SRB activity is mostly confined to aquifer sands. Vertical diffusion and advection were modeled to estimate acetic acid transport from aquitard to aquifer. Assuming that SRB completely respire the acetic acid transported into the aquifer (3.2 μmol·l−1·m·a−1), the CO2 production rate in the aquifer sands is 5.3 μmol·l−1·a−1. This slow mineralization rate of in situ organic matter is within the range for deep aquifers, and probably accounts for the long-term survival of microorganisms in oligotrophic environments. Finally, the microbial communities in Yegua sediments appear to exhibit a loose commensalism, with microorganisms in aquitards providing VOAs for respiratory processes (i.e., SO4 reduction) in aquifers.
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| 23. |
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| 24. |
- Thoss, A., et al.
(author)
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Kilohertz sources of hard x rays and fast ions with femtosecond laser plasmas
- 2003
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In: Journal of the Optical Society of America. B, Optical physics. - 0740-3224 .- 1520-8540. ; 20:1, s. 224-228
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Journal article (peer-reviewed)abstract
- We demonstrate a new, stable, kilohertz femtosecond laser plasma source of hard-x-ray continuum and K-alpha emission that uses a microscopic liquid jet target that is continuous and debris free. Plasmas produced by ultrashort (50-fs) intense laser pulses from a fine (10-30-mum diameter) liquid Ga jet emit bright 9.3- and 10.3-keV K-alpha and K-beta lines superimposed on a multikilovolt bremmstrahlung continuum. Kilohertz femtosecond x-ray sources will find many applications in time-resolved x-ray diffraction and microscopy studies. As high-intensity lasers become more compact and operate at increasingly high repetition-rates, they require a target configuration that is both repeatable from shot to shot and debris free. Our target provides a pristine, unperturbed filament surface at rates >100 kHz. A number of liquid metal targets are considered. We show the hard-x-ray spectrum described above. The source was generated by a 50-fs-duration, 1-kHz, 2-W, high-intensity Ti:sapphire laser. Using the same technology, we also generate forward-going sub-mega-electron-volt (sub-MeV) protons from a 10-mum liquid water target at 1-kHz repetition rates. Kilohertz sources of high-energy ions will find many applications in time-resolved particle interaction studies and will lead to efficient generation of short-lived isotopes for use in nuclear medicine and other applications. The protons were detected with CR-39 track detectors in both the forward and the backward directions up to energies of similar to500 keV. As the intensity of compact high-repetition-rate lasers sources increases, we can expect improvements in the energy, conversion efficiency, and directionality to occur. The effect of these developments is discussed. As compact, high-repetition-rate femtosecond laser technology reaches focused intensities of similar to10(19) W/cm(2), many new applications of high-repetition-rate hard-x-ray and MeV ion sources will become practical.
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| 25. |
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