24,531 research outputs found
Tumor-specific activity of cellular regulatory elements is down-regulated upon insertion into the herpes simplex virus genome
No full textTranscriptional targeting of viral genes is a promising strategy to achieve tumor-specific replication of oncolytic viruses. Due to its natural tropism, herpes simplex virus type 1 (HSV-1) may be an ideal tool for oncolytic therapy of brain tumors such as malignant glioblastoma. To study whether glioma-specific gene expression can be accomplished within the HSV-1 genome, four cellular regulatory elements were exemplarily studied. Whereas the human telomerase reverse transcriptase (hTERT) and survivin promoters and the nestin and vascular endothelial growth factor A (VEGF-A) enhancers displayed pronounced glioma specificity after plasmid transfection, only the nestin enhancer conferred a certain selectivity for glioma cells and notable activity when transferred into the viral genome. The nestin enhancer was also found to be highly useful for tumor cell-specific expression of a therapeutically relevant gene (interleukin-2) when tested in combination with the hTERT or simian virus 40 (SV40) early promoter in the HSV-1 genome. Because activity of the chosen promoter in a tumor is a prerequisite for the successful application of an oncolytic virus, we examined whether the activity of a promoter can be deduced from the amounts of cellular mRNA or protein expressed under its control. We found little correlation between promoter activity and mRNA levels of the corresponding gene, whereas protein expression was more closely related to promoter activity. We conclude that the cellular elements are differently regulated in the viral and cellular genomes. Mechanistic insight into the differential regulation is required to improve and refine the design of transcriptionally targeted HSV vectors. Journal of NeuroVirology (2008) 14, 522-535
Characterization of the murine cytomegalovirus genes encoding the major DNA binding protein and the ICP18.5 homolog
No full textIn several herpesviruses the genes for the major DNA binding protein (MDBP), a putative assembly protein, the
glycoprotein B (gB), and the viral DNA polymerase (pol) coliocate. In murine cytomegalovirus (MCMV), two members
of this gene block, pol (Elliott, Clark, Jaquish, and Spector, 1991, Virology 185, 169-186) and gB (Rapp, Messerle,
BOhler, Tannheimer, Keil, and Koszinowski, 1992, J. Virol., 66,4399-4406) have been characterized. Here the two other
MCMV genes are characterized, the gene encoding the MDBP and the ICP18.5 homolog encoding a putative
assembly protein. Like in human cytomegalovirus (HCMV) the genes order is pol, gB, ICP18.5, and MDBP. The 4.2-kb
MDBP mRNA is expressed first in the early phase, whereas the 3.0-kb ICP18.5 mRNA is a late transcript. The open
reading frame of the MDBP gene has the capacity of encoding a protein of 1191 amino acids with a predicted molecular
mass of 131.7 kDa. The MCMV ICP18.5 ORF is translated into a polypeptide of 798 amino acids with a calculated
molecular mass of 89.1 kDa. Comparison of the amino acid sequences of the predicted proteins of MCMV with the
respective proteins of HCMV, Epstein-Barr virus (EBV), and herpes simplex virus type-1 (HSV-1) reveals a striking
homology ranging from 72% (HCMV), 50% (EBV), to 45% (HSV-1) for the MDBP sequence and from 74% (HCMV), 51 %
(EBV), to 49% (HSV-1) for the ICP18.5 sequence. These results establish the elose relationship of the two cytomegaloviruses,
and underline the usefulness of the murine model for studies on the biology of the CMV infection
A redshifted codon-optimized firefly luciferase is a sensitive reporter for bioluminescence imaging
No full textBioluminescence imaging has evolved as a powerful tool for monitoring biological processes in vivo. As transmission efficiency of light through tissue increases greatly for wavelengths above 600 nm we examined whether a redshifted codon-optimized firefly luciferase (lambda(max) = 615 nm) could be successfully employed as a sensitive reporter in mammalian cells. To this end, unmodified codon-optimized luciferase ( lmax = 557 nm) as well as the red-emitting S284T mutant luciferase were expressed simultaneously in human glioma cells in vitro as well as in quadriceps muscles of mice in vivo. We show here that activity of the redshifted enzyme in human glioma cell culture approached approximately one-fourth of that seen with the unmodified enzyme. In contrast, light emission by the red-emitting luciferase in vivo was generally more efficient than that produced by its unmodified counterpart, most likely due to reduced absorption of red light by tissue. The mean ratio of light emission produced by the redshifted luciferase to that of the unmodified enzyme in vivo was similar to 3. Application of this new redshifted luciferase together with other optical reporters may be of considerable importance to biological research as it allows for imaging of deeper tissues as well as simultaneous monitoring of two molecular events in vitro and in vivo if appropriate filter sets are employed
Jack Alive / Martin Dead : The Location of the "Author" in Jack London\u27s Martin Eden
No full textThis essay is an attempt to read Martin Eden, Jack Londonʼs autobiographical novel, in terms of the inextricable relationship between the author and the protagonist. Critics have often taken the unbalanced plot and the lack of ironic distance between narrator and character in Martin Eden as the technical weakness of London, but this paper argues that the achievement of this novel owes a great deal to the attachment of London to Martin. The unbalanced structure is a necessary product of the severe struggle of the author to kill his romantic alter ego. // Martin, who aspires to win Ruth Morse, tries to cross class boundaries by making a career of a writer. Even after realizing the emptiness of Ruth, who turns out to be nothing but a typical figure of the bourgeoisie, he somehow persists in loving her. The notion underlying here is that, for Martin, love, career and art are fundamentally inseparable. He objects to the aestheteʼs view of Brissenden on account of his separation of art from career. Martinʼs identity and life consist only in the triunity of love/career/art; the alternative is the repudiation of life. Thus, the unnatural delay of his disappointment in love can be regarded as Londonʼs strategy to set the suicide of Martin as the necessary consequence of the story. // By finishing the story and killing Martin, London finally detaches himself from Martin, reconstructs his self, and, unlike Martin, survives as a professional writer. In this sense, Martin Eden is a story about “writerʼs self-reconstruction.
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Letter from Martin Chizzick
No full textCongratulations to Duane Pearsall for receiving the Enterpreneur of the Year award; note on the letter was written by Pearsall and it mentions that Martin, the author of the letter, died in a airplane accident
Robert Martin Tiffin's Mystery Man Newspaper Articles
No full textAdvertiser-Tribune newspaper clippings featuring a story about Robert Martin (written by Nancy Kleinhenz), a local author from Tiffin (Ohio) who wrote under the pseudonym of Lee Roberts, and two of his short stories. Martin wrote mystery novels in his spare time, creating more than 22 mystery novels. For more information about Robert Martin and a list of books go to http://www.mysteryfile.com/RMartin/JBennett.html
An acidic region of the 89K murine cytomegalovirus immediate early protein interacts with DNA
No full textThe product of the ie 1 gene, the regulatory immediate early protein pp89 of murine cytomegalovirus (MCMV), interacts with core histones, which can mediate the association of pp89 with DNA. We report the capacity of pp89 to interact directly with DNA in the absence of cellular proteins. After separation of proteins by SDS–PAGe, pp89 bound ds- and ssDNA, with a preference for ssDNA. Binding to specific DNA sequences in the MCMV genome was not detected. The DNA-binding region of pp89 was located to amino acids 438 to 534 by analysis of deletion mutants expressed as -galactosidase or TrpE fusion proteins. This region is identical to the highly acidic C-terminal region spanning amino acids 424 to 532. The human cytomegalovirus IE1 protein, which contains a similar extended C-terminal acidic region, does not react with DNA under the same experimental conditions
Structural organization, expression, and functional characterization of the murine cytomegalovirus immediate-early gene 3.
No full textWe have previously defined ie3 as a coding region located downstream of the ie1 gene which gives rise to a 2.75-kb immediate-early (IE) transcript. Here we describe the structural organization of the ie3 gene, the amino acid sequence of the gene product, and some of the functional properties of the protein. The 2.75-kb ie3 mRNA is generated by splicing and is composed of four exons. The first three exons, of 300, 111, and 191 nucleotides (nt), are shared with the ie1 mRNA and are spliced to exon 5, which is located downstream of the fourth exon used by the ie1 mRNA. Exon 5 starts 28 nt downstream of the 3' end of the ie1 mRNA and has a length of 1,701 nt. The IE3 protein contains 611 amino acids, the first 99 of which are shared with the ie1 product pp89. The IE3 protein expressed at IE times has a relative mobility of 88 kDa in gels, and a mobility shift to 90 kDa during the early phase is indicative of posttranslational modification. Sequence comparison reveals significant homology of the exon 5-encoded amino acid sequence with the respective sequence of UL 122, a component of the IE1-IE2 complex of human cytomegalovirus (HCMV). This homology is also apparent at the functional level. The IE3 protein is a strong transcriptional activator of the murine cytomegalovirus (MCMV) e1 promoter and shows an autoregulatory function by repression of the MCMV ie1/ie3 promoter. The high degree of conservation between the MCMV ie3 and HCMV IE2 genes and their products with regard to gene structure, amino acid sequence, and protein functions suggests that these genes play a comparable role in the transcriptional control of the two cytomegaloviruses
Experiences Using Large Scale Video Walls for Distance Education
No full textWe describe our experiences building and using the Rutgers Videowall, a low-cost telepresence system that has been used teaching 15 courses and colloquia. By relaxing typical spatial telepresence features, such as background continuity, we greatly reduced costs and gained flexibility in the rooms it could be deployed in. The lower costs and room flexibility enabled academic departments to use the wall, in contrast to traditional telepresence systems which remained inaccessible. We found that the Videowall’s spatial distortions did not have a significant impact on useability, as our initial survey results show that students had an overall positive experience.Technical report DCS-tr-72
Hans Martin Schwarz Collection 1934 - 1938
No full textThis collection contains clippings of articles by Hans Martin Schwarz (1917, Hamburg – 2006, New York, better known as Martin Ebon), published between 1934 and 1938 in German-Jewish newspapers on a wide variety of subjects such as sports, emigration, the political situation in Germany, and religious attitudes of the young. It also contains reviews of his books "Einer wie Du und Ich" and "Heiteres, Besinnliches, Nachdenkliches."digitizedHans Martin Schwarz (1917, Hamburg – 2006, New York, better known as Martin Ebon), was a journalist and author. In Germany during the 1930s, he published in a variety of German-Jewish periodicals, primarily the Israelitisches Familienblatt. After immigrating to the United States in 1938, he changed his name to Martin Ebon, and published dozens of books in the areas of world affairs and parapsychology.Processe
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