8,069 research outputs found
Human herpesvirus 8 cellular gene modulation
P0663 Human herpesvirus 8 cellular gene modulation
Barbara Matteoli*
1
, Rita Romano
2
,FrancescaTabacchi
2
, Moreno Ferroni
1
1 LAMM,SRL,Lucca, Italy,
2 Department of Public Health and Infectious Diseases,Sapienza University of Rome,
Rome, Italy
Background:Sinceinflammation is the basis of viral pathogenesis and may beinduced either directly by thevirus
or by thecell in responseto infection, theexpression pattern of cellular genes involved in this process was
investigated in human epithelial and lymphoid cells infected with Human herpes virus 8 (HHV8) .
Materials/methods:Theexpression of 297 human genes involved in 65 pathways associated with inflammation
have been studied in HEK293 and PBMC cells 24h after infection with HHV8 (A1 and C3 strains) by DualChip
Microarray.Signal quantification was performed by SilverQuant Image Viewer and analysis software(Eppendorf,
Germany) and SPSS 16.0 for Windows (SPSS, USA) with two way ANOVA followed by Scheffecontrast.
Results:Expression ratios of most of the genes werecloseto 1 or changed only <2-fold cutoff (in positive or
negativevalue), suggesting that they were not significantly changed in consequenceto HHV8 infection. Overall,a
higher number of genes resulted modulated in HHV8-infected HEK293 cells with respect to PBMCs. A robust
increasein theexpression was found in genes involved in inflammation (i.e., AGT, CCR8, CXCR4, IL-6, IL-9, IL10RA,
IL-17, IL-23A), signal transduction (i.e.,FGF5,FGF7, MAP3K1, MAPk9m TGFBR1,TRAF2),cellular cycle(IGFBP1),
immuneresponse(i.e., IL-16,TLR4),apoptosis (TNFSF4,TNFSF11),and others genes belonging to different
categories (i.e., BMP4, BMPR2,EPHA3, HGFBP1, RUNX1, RUNX2,SP1).With a >2-fold threshold filter gene
modulation as significant,a high numbers of genes resulted significantly modulated both in HEK293 cell lineand
PBMCs infected both with the A1 (169 and 104 genes, respectively) and C3 subtypes (131 and 93 genes,
respectively). Next, to increasethesignificance, only those genes with >4-fold changes in their expression were
considered. A total of 24 genes resulted strongly induced,especially after A1 subtypeinfection.Thecomparison of
transcriptional profiling between both viral subtypes showed that only 4 genes arestrongly induced by different
viral subtypes (i.e., BMP4, BMPR2, RUNX2 and TNFSF11).
Conclusions: New human genes have been involved in HHV8 infection;commonly modulated genes may be
used as target for antiviral/chemiotherapic treatmen
“Modulazione dell'espressione genica in cellule linfoidi ed epitelioidi infettate con il Virus Erpetico Umano 8 (HHV8) ed analisi dell’attività chemioterapica/antivirale della Distamicina A (DA)”
Purpose of this PhD study have been the analysis of the modulation of cellular gene by Human Herpes virus 8 (HHV8) infection and of the potential antiviral effect of Distamycin A (DA), an oligopeptidic antibiotic. This study describes a comprehensive picture of global gene changes soon after HHV-8 active infection of two susceptible cell types. We found that host cell expression changes after only 24 hours of infection, and it is quite different from previous gene induction studies that were carried out at later time points of virus infection. In fact, Poole et al. have used a different primary effusion lymphoma cell line (JSC1) to produce the virus that was used to infect primary endothelial cells for a period of 3–5 weeks, and gene array experiments were done when almost all of the cells changed from typical cobblestone to spindle-shaped morphology and were positive for LANA. Several features were apparent from these analysis: a) there was virtually non-overlapping list of genes in all of two viral subtypes analyzed; b) HHV-8-induced transcriptional profiles in the epithelial and PBMC were closely different. This is probably because the criteria of > 4-fold gene induction as significant is a threshold filter very tight. Nevertheless, the genes that emerge from such comparison will be of greater interest for studying their role in the unique biology of HHV-8. Furthermore, the replicative capacity of the two different strains in the two cell types and the modulation of cell involved in the inflammatory process would seem to indicate that the genotypic difference could be translated into a different virus-host relationship, also attributable to a different pathogenetic mechanism. In addition to identifying specific host response genes within each functional pathway that are already known to be important for HHV-8 infection, our findings identify novel candidate genes that are not yet known in HHV-8 biology.
Obtained results show a lack of cytotoxicity of DAlipo on cultured HEK293, RCE and PBMC cells. It might be noted that the CC50 value found in the present study falls at the low extreme of the range of CC50 values reported in the literature. In fact, available data show CC50 values ranging from 35 μM in a Hep-2 cell line to 154 μM in a HeLa cell line and 385 μM in rabbit primary kidney cells. It has been reported that DA inhibits the activity of all DNA polymerases. This mechanism of action could explain its antiviral activity. Because of the lack of information concerning the relevant genetic definition of HHV8 A1 and C3 subtypes from BCBL1 and BC3 cell lines, whether the observed behavior be the result of the expression of specific mutated genes or a non specific consequence of viral strain virulence has to be established. Clearly, further studies are needed to explain the different degree of sensitivity of HHV8 subtypes to DA and Dalipo. The significant antiviral activity of DAlipo and the lack of citotoxicity in epithelial and lymphoid cell lines shown in the present study indicates the compound as an antiherpetic drug potentially useful in both topic and systemic treatments. It could be used either alone or in association with other antiviral treatment, the latter to be employed at lower dosages and for shorter periods of time, thus limiting side effects. The antiviral activity of DAlipo formulation also in lymphoid cell lines may be due to the hydrophobic or amphiphilic drug penetration efficacy increased through inclusion of the drug in liposomes. DAlipo showed, when compared with the free drug, higher antiviral activity against HHV8 A1 and C3 subtypes in PBMCs and might therefore represent a promising DA formulation that could be used also for systemic treatments
Barbara James
Date:1943Barbara was born in Holdredge, Nebraska in the United States of America in 1943. In 1960 she arrived in Darwin working in a variety of occupations such as a journalist, historian, author, activist, advocate and editor. Barbara wrote 13 books including "No Man's Land" which explored the contributions of women in the Northern Territory. She also received a number of awards including 2001 NT Heritage Award, the 2000 NT Literary Essay Awards and the Chief Minister's Women's Achievement Award in 1999.JournalistHistorianAuthorActivistEditorAmerica
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The collection includes files related to the publication: Barbara Szczepańska, Post‐War Architecture and Urban Planning as Means of Reinventing Opole’s Past and Identity, „Urban Planning”, Vol 8, No 1 (2023): Bombed Cities: Legacies of Post-War Planning on the Contemporary Urban and Social Fabric, pp. 266-278, https://doi.org/10.17645/up.v8i1.6079. The collection includes figures used in the publication:Opole_plan A plan of Opole, with areas of Ostrówek (left), Market Square (center) and Central Square (right) highlighted in red. Originally published in: "Guidebook to the city of Opole" ("Przewodnik po mieście Opolu", Opole: Księgarnia Opolska, 1948, https://polona.pl/preview/2f383a4a-5e9e-444d-9e94-366b8ac8610d). Author: Z. Streer. Licence: CC0Opole_Monument to the Opole Silesian Fighters for Freedom A photograph depicting Monument to the Opole Silesian Fighters for Freedom (Pomnik Bojownikom o Wolność Śląska Opolskiego) in Opole. Author: Barbara Szczepańska. Licence: CC0Opole_monument of Kazimierz I Opolczyk A photograph depicting the monument of Kazimierz I Opolczyk in the Market Square in Opole. Author: Barbara Szczepańska. Licence: CC0Opole_Market Square_eastern frontage A photograph depicting eastern frontage of the Market Square in Opole. Author: Barbara Szczepańska. Licence: CC0Opole_Market Square_eastern frontage_before 1945 A photograph depicting eastern frontage of the Market Square in Opole before 1945. Originally published on Wikimedia Commons: https://commons.wikimedia.org/wiki/File:Market_Square_in_Opole,_eastern_frontage.jpg. Author: unknown. Licence: CC0Opole_monument of Frederick the Great A photograph depicting monument of Frederick the Great in Opole, before 1945. Originally published on Wikimedia Commons: https://commons.wikimedia.org/wiki/File:Opole_Oppeln_Denkmal_Friedrich_der_Große.jpg. Author: unknown. Licence: CC0</ul
'A date with Barbara': paracosms of the self in biographies of Barbara Newhall Follett
In 1927, 13-year-old Barbara Newhall Follett published her first book, the critically acclaimed novel, The House Without Windows and Eepersip's Life There.
Twelve years later, on December 7, 1939, 25-year-old Barbara quarrelled with her husband and left her apartment in Boston with $30 in her pocket, and a notebook. She was never seen again.
The House Without Windows is set in a paracosm (Farksolia) she invented, and ends with the metamorphosis of the titular character into a 'fairy-a wood nymph … invisible for ever to all mortals, save those few who have minds to believe, eyes to see'.
In Barbara's (auto)biography, The Unconscious Autobiography of a Child Genius (1966), written by Harold Grier McCurdy 'in collaboration with Helen Follett' (Barbara's mother), the authors wonder: 'Can we be far wrong in substituting Barbara's name for Eepersip's in the closing scenes of [House Without Windows]?
In this paper, I grapple with the formal and ethical challenges of writing about Barbara Newhall Follett, and the ways her family and others have approached the problem of writing her unresolved life story: a child raised and educated in solitude, a celebrated 'natural' child author, a young woman whose disappearance remains unsolved. The paper will explore the ways in which adults write the stories of children's lives, as nostalgia and fable, as fairytale and paracosmic narrative, and the ways in which Barbara's biographers have, consciously and unconsciously, created biographical concordances, or paracosms of the self, in seeking to make meaning of her life's story
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