2,379 research outputs found
Binding of the heterogeneous ribonucleoprotein K (hnRNP K) to the Epstein-Barr virus nuclear antigen 2 (EBNA2) enhances viral LMP2A expression.
No full textThe Epstein-Barr Virus (EBV) -encoded EBNA2 protein, which is essential for the in vitro transformation of B-lymphocytes, interferes with cellular processes by binding to proteins via conserved sequence motifs. Its Arginine-Glycine (RG) repeat element contains either symmetrically or asymmetrically di-methylated arginine residues (SDMA and ADMA, respectively). EBNA2 binds via its SDMA-modified RG-repeat to the survival motor neurons protein (SMN) and via the ADMA-RG-repeat to the NP9 protein of the human endogenous retrovirus K (HERV-K (HML-2) Type 1). The hypothesis of this work was that the methylated RG-repeat mimics an epitope shared with cellular proteins that is used for interaction with target structures. With monoclonal antibodies against the modified RG-repeat, we indeed identified cellular homologues that apparently have the same surface structure as methylated EBNA2. With the SDMA-specific antibodies, we precipitated the Sm protein D3 (SmD3) which, like EBNA2, binds via its SDMA-modified RG-repeat to SMN. With the ADMA-specific antibodies, we precipitated the heterogeneous ribonucleoprotein K (hnRNP K). Specific binding of the ADMA- antibody to hnRNP K was demonstrated using E. coli expressed/ADMA-methylated hnRNP K. In addition, we show that EBNA2 and hnRNP K form a complex in EBV- infected B-cells. Finally, hnRNP K, when co-expressed with EBNA2, strongly enhances viral latent membrane protein 2A (LMP2A) expression by an unknown mechanism as we did not detect a direct association of hnRNP K with DNA-bound EBNA2 in gel shift experiments. Our data support the notion that the methylated surface of EBNA2 mimics the surface structure of cellular proteins to interfere with or co-opt their functional properties
Epstein-Barr virus latent proteins regulate expression of the anti-apoptotic cellular bfl-1 gene
No full textThe ubiquitous and oncogenic human herpes-virus Epstem-Barr virus (EB V) establishes a latent infection and promotes the long-term survival of the infected host cell by targeting the molecular machinery that controls cell fate decisions, including apoptosis, proliferation and differentiation. These host-virus interactions are likely to play a crucial role in the development of EBV-associated malignancies such, as Burkitt’s lymphoma, Hodgkin’s disease, nasopharyngeal carcinoma and tumours in lmmunosuppressed individuals. It has previously been shown in our laboratory that two EBV latent proteins, latent membrane protein 1 (LMP1) and EBV nuclear antigen 2 (EBNA2), which are major effectors of cellular phenotypic change, can independently regulate expression of the cellular bfl-1 gene Bfl-1 is an anti-apoptotic protein of the Bcl-2 family, whose preferential expression in hematopoietic and endothelial cells is controlled by inflammatory stimuli. In this study, it is reported that LMP1 and EBNA2 regulate bfl-1 activity through interactions with components of the NF-kB and Notch signalling pathways respectively NF-kB composed of p65 sub-units trans-activated the bfl-1 promoter m the EBV-negative cell line DG75, and an NF-icB-like binding site at position -52 to -43 relative to the transcription start site was essential for this effect. An RBP-Jk/CBF1 mutant blocked EBNA2-mediated trans-activation of bfl-1 in DG75 cells, indicating an important role for this DNA-binding protein in bfl-1 trans-activation by EBNA2. Although RBP-Jk/CBFI is also essential for signalling by the cellular equivalent of EBNA2, mtra-cellular Notch (NotchIC), this protein was not found to trans-activate the bfl-1 promoter. Both EBNA2 and LMP1 are expressed in EBVmfected cell lines, and EBNA2 is responsible for induction of LMP1 Blocking of either EBNA2- or LMP1-mediated signalling in EBV-mfected cell lines did not dramatically affect the level of bfl-1 promoter activity. However, when both EBNA2 and LMP1 signalling were blocked simultaneously, a significant decrease in the level of bfl-1 activity was observed. These data indicate a role for both EBNA2 and LMP1 in the regulation of the promoter for the bfl-1 gene m the context of the EBV-infected cell. These findings are relevant to our understanding of EBV persistence in the infected host, and its role in malignant disease
Identification and Functional Analysis of Epstein-Barr Nuclear Antigen 2 (EBNA2) Target Genes
No full textMeeting with the Hebrew author Elias Hurwitz
No full textWhite paper; handpainted; on the reverse of Luftwaffe uniform pattern. Digitized posters are related to the activities of Jewish displaced persons drawn from the Records of Displaced Persons Camps and Centers in Germany (RG 294.2) Italy (RG 294.3) and Austria (RG 294.4) held by YIVO Archives. Please consult the historical note for those record groups for further information.Digital ImageDigital finding aid available
Obituary announcement about author and labor activist Sh. Mendelson
No full textBrown paper; handpainted. Digitized posters are related to the activities of Jewish displaced persons drawn from the Records of Displaced Persons Camps and Centers in Germany (RG 294.2) Italy (RG 294.3) and Austria (RG 294.4) held by YIVO Archives. Please consult the historical note for those record groups for further information.Digital ImageDigital finding aid available
A spectroscopic study of unstable species in the gas phase
No full textThis thesis contains the results of spectroscopic investigations on several unstable gas phase species. Two techniques were used: photoelectron spectroscopy with a synchrotron photon source, and resonance enhanced raultiphoton ionization (REMPI) spectroscopy. Chapter 1 contains an introduction to the photoelectron and REMPI spectroscopic techniques. In Chapter 2 the experimental apparatus used for the study of short lived molecules with photoelectron spectroscopy using synchrotron radiation is described. Chapter 3 outlines the fundamental principles of photoelectron spectroscopy using both fixed and tunable wavelength radiation such as that found at a synchrotron source. In Chapter 4 photoionization of the OH and OD radicals, produced from the H + NO; and D + NO2 reactions, has been studied in the photon energy region 13.0-17.0 eV. A comparison of vibrationally specific OH and OD CIS spectra, and photoelectron spectra recorded at resonant wavelengths, has allowed a more complete assignment of structure observed in earlier photoionization mass spectrometric measurements. These assignments have been supported by the results of Franck-Condon calculations. Photoelectron spectra recorded for the first bands of OH and OD at resonant photon energies have allowed more extensive vibrational structure to be obtained than has previously been recorded by PES experiments performed with inert gas discharge photon sources. In Chapter 5 the photoionization behaviour of OaCa'Ag) is studied in the photon energy region 12.5-19.0 eV. Suggestions are made for the nature of the highly excited states of O2 associated with the observed structure in the CIS spectra, based on available ionization energies and spectroscopic constants of known ionic states accessible from 02(a^Ag). In Chapter 6 the experimental apparatus used in the REMPI spectroscopic studies of Ar NO, Kr-NO and (CO): is described. Chapter 7 contains the details of the theoretical models used to interpret the (2+1) REMPI spectra of rare gas-NO (Rg NO) complexes. In Chapter 8 the results of REMPI studies on the Ar NO and Kr-NO van der Waals complexes are presented. For both complexes significant deviation from a T-shaped structure is found in their excited states, although it was not possible to determine the absolute position of the rare gas atom within experimental uncertainty. From the REMPI spectra dissociation energies of 582 and 803 cm'^ were derived for the E^E'" states of Ar NO and Kr-NO respectively. Chapter 9 describes the results of preliminary REMPI studies on (CO):. Chapter 10 describes a statistical technique for determining the number of ions contained in an ion trap mass spectrometer In Chapter 11 conclusions are drawn from the work presented in this thesis and suggestions for further work are made.</p
Neighborhood Poverty and the Resurgence of Tuberculosis in New York City, 1984 to 1992
No full texthttp://deepblue.lib.umich.edu/bitstream/2027.42/56185/1/Barr RG, Neighborhood Poverty and the Resurgence of Tuberculosis in New York City, 1984 to 1992, 2001.pd
Sweeping has no effect on renormalized turbulent viscosity
No full textWe perform renormalization group analysis (RG) of the Navier-Stokes equation in the presence of constant mean velocity field , and show that the renormalized viscosity is unaffected by , thus negating the ``sweeping effect", proposed by Kraichnan [Phys. Fluids {\bf 7}, 1723 (1964)] using random Galilean invariance. Using direct numerical simulation, we show that the correlation functions for and differ from each other, but the renormalized viscosity for the two cases are the same. Our numerical results are consistent with the RG calculations
Utilising proteomic approaches to understand oncogenic human herpesviruses
No full textThe γ‑herpesviruses Epstein-Barr virus and Kaposi's sarcoma‑associated herpesvirus are successful pathogens, each infecting a large proportion of the human population. These viruses persist for the life of the host and may each contribute to a number of malignancies, for which there are currently no cures. Large‑scale proteomic-based approaches provide an excellent means of increasing the collective understanding of the proteomes of these complex viruses and elucidating their numerous interactions within the infected host cell. These large‑scale studies are important for the identification of the intricacies of viral infection and the development of novel therapeutics against these two important pathogens
Antibodies against the mono-methylated arginine-glycine repeat (MMA-RG) of the Epstein-Barr virus nuclear antigen 2 (EBNA2) identify potential cellular proteins targeted in viral transformation.
No full textThe Epstein-Barr virus is a human herpes virus with oncogenic potential. The virus-encoded nuclear antigen 2 (EBNA2) is a key mediator of viral tumorigenesis. EBNA2 features an arginine-glycine (RG) repeat at amino acids (aa)339-354 that is essential for the transformation of lymphocytes and contains symmetrically (SDMA) and asymmetrically (ADMA) di-methylated arginine residues. The SDMA-modified EBNA2 binds the survival motor neuron protein (SMN), thus mimicking SMD3, a cellular SDMA-containing protein that interacts with SMN. Accordingly, a monoclonal antibody (mAb) specific for the SDMA-modified RG repeat of EBNA2 also binds to SMD3. With the novel mAb 19D4 we now show that EBNA2 contains mono-methylated arginine (MMA) residues within the RG repeat. Using 19D4, we immune-precipitated and analysed by mass spectrometry cellular proteins in EBV-transformed B-cells that feature MMA motifs that are similar to the one in EBNA2. Among the cellular proteins identified, we confirmed by immunoprecipitation and/or Western blot analyses Aly/REF, Coilin, DDX5, FXR1, HNRNPK, LSM4, MRE11, NRIP, nucleolin, PRPF8, RBM26, SMD1 (SNRDP1) and THRAP3 proteins that are either known to contain MMA residues or feature RG repeat sequences that probably serve as methylation substrates. The identified proteins are involved in splicing, tumorigenesis, transcriptional activation, DNA stability and RNA processing or export. Furthermore, we found that several proteins involved in energy metabolism are associated with MMA-modified proteins. Interestingly, the viral EBNA1 protein that features methylated RG repeat motifs also reacted with the antibodies. Our results indicate that the region between aa 34-52 of EBNA1 contains ADMA or SDMA residues, while the region between aa 328-377 mainly contains MMA residues
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