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Article ; Online: Three New Derivatives of Zopfinol from

Harms, Karen / Milic, Andrea / Stchigel, Alberto M / Stadler, Marc / Surup, Frank / Marin-Felix, Yasmina

2021 Volume 7, Issue 3

Abstract: Triangularia ... ...

Abstract	Triangularia mangenotti
Language	English
Publishing date	2021-03-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2784229-0
ISSN	2309-608X ; 2309-608X
ISSN (online)	2309-608X
ISSN	2309-608X
DOI	10.3390/jof7030181
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Article ; Online: Decoding murine cytomegalovirus.

Lodha, Manivel / Muchsin, Ihsan / Jürges, Christopher / Juranic Lisnic, Vanda / L'Hernault, Anne / Rutkowski, Andrzej J / Prusty, Bhupesh K / Grothey, Arnhild / Milic, Andrea / Hennig, Thomas / Jonjic, Stipan / Friedel, Caroline C / Erhard, Florian / Dölken, Lars

PLoS pathogens

2023 Volume 19, Issue 5, Page(s) e1010992

Abstract: The genomes of both human cytomegalovirus (HCMV) and murine cytomegalovirus (MCMV) were first sequenced over 20 years ago. Similar to HCMV, the MCMV genome had initially been proposed to harbor ≈170 open reading frames (ORFs). More recently, omics ... ...

Abstract	The genomes of both human cytomegalovirus (HCMV) and murine cytomegalovirus (MCMV) were first sequenced over 20 years ago. Similar to HCMV, the MCMV genome had initially been proposed to harbor ≈170 open reading frames (ORFs). More recently, omics approaches revealed HCMV gene expression to be substantially more complex comprising several hundred viral ORFs. Here, we provide a state-of-the art reannotation of lytic MCMV gene expression based on integrative analysis of a large set of omics data. Our data reveal 365 viral transcription start sites (TiSS) that give rise to 380 and 454 viral transcripts and ORFs, respectively. The latter include >200 small ORFs, some of which represented the most highly expressed viral gene products. By combining TiSS profiling with metabolic RNA labelling and chemical nucleotide conversion sequencing (dSLAM-seq), we provide a detailed picture of the expression kinetics of viral transcription. This not only resulted in the identification of a novel MCMV immediate early transcript encoding the m166.5 ORF, which we termed ie4, but also revealed a group of well-expressed viral transcripts that are induced later than canonical true late genes and contain an initiator element (Inr) but no TATA- or TATT-box in their core promoters. We show that viral upstream ORFs (uORFs) tune gene expression of longer viral ORFs expressed in cis at translational level. Finally, we identify a truncated isoform of the viral NK-cell immune evasin m145 arising from a viral TiSS downstream of the canonical m145 mRNA. Despite being ≈5-fold more abundantly expressed than the canonical m145 protein it was not required for downregulating the NK cell ligand, MULT-I. In summary, our work will pave the way for future mechanistic studies on previously unknown cytomegalovirus gene products in an important virus animal model.
MeSH term(s)	Animals ; Mice ; Humans ; Muromegalovirus ; Cytomegalovirus/genetics ; Cytomegalovirus/metabolism ; Base Sequence ; Viral Proteins/genetics ; Viral Proteins/metabolism ; Open Reading Frames
Chemical Substances	Viral Proteins
Language	English
Publishing date	2023-05-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7374
ISSN (online)	1553-7374
ISSN	1553-7374
DOI	10.1371/journal.ppat.1010992
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Article ; Online: The HSV-1 ICP22 protein selectively impairs histone repositioning upon Pol II transcription downstream of genes.

Djakovic, Lara / Hennig, Thomas / Reinisch, Katharina / Milić, Andrea / Whisnant, Adam W / Wolf, Katharina / Weiß, Elena / Haas, Tobias / Grothey, Arnhild / Jürges, Christopher S / Kluge, Michael / Wolf, Elmar / Erhard, Florian / Friedel, Caroline C / Dölken, Lars

Nature communications

2023 Volume 14, Issue 1, Page(s) 4591

Abstract: Herpes simplex virus 1 (HSV-1) infection and stress responses disrupt transcription termination by RNA Polymerase II (Pol II). In HSV-1 infection, but not upon salt or heat stress, this is accompanied by a dramatic increase in chromatin accessibility ... ...

Abstract	Herpes simplex virus 1 (HSV-1) infection and stress responses disrupt transcription termination by RNA Polymerase II (Pol II). In HSV-1 infection, but not upon salt or heat stress, this is accompanied by a dramatic increase in chromatin accessibility downstream of genes. Here, we show that the HSV-1 immediate-early protein ICP22 is both necessary and sufficient to induce downstream open chromatin regions (dOCRs) when transcription termination is disrupted by the viral ICP27 protein. This is accompanied by a marked ICP22-dependent loss of histones downstream of affected genes consistent with impaired histone repositioning in the wake of Pol II. Efficient knock-down of the ICP22-interacting histone chaperone FACT is not sufficient to induce dOCRs in ΔICP22 infection but increases dOCR induction in wild-type HSV-1 infection. Interestingly, this is accompanied by a marked increase in chromatin accessibility within gene bodies. We propose a model in which allosteric changes in Pol II composition downstream of genes and ICP22-mediated interference with FACT activity explain the differential impairment of histone repositioning downstream of genes in the wake of Pol II in HSV-1 infection.
MeSH term(s)	Humans ; Histones/metabolism ; Herpesvirus 1, Human/genetics ; Transcription, Genetic ; Viral Proteins/genetics ; Viral Proteins/metabolism ; Herpes Simplex/genetics ; Chromatin/genetics ; Chromatin/metabolism ; Immediate-Early Proteins/genetics ; Immediate-Early Proteins/metabolism
Chemical Substances	Histones ; Viral Proteins ; Chromatin ; ICP22 protein, human herpesvirus 1 ; Immediate-Early Proteins
Language	English
Publishing date	2023-07-31
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-40217-w
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Article ; Online: Three New Derivatives of Zopfinol from Pseudorhypophila Mangenotii gen. et comb. nov

Harms, Karen / Milic, Andrea / Stchigel, Alberto M / Stadler, Marc / Surup, Frank / Marin-Felix, Yasmina

7 ; 3 ; Journal of fungi (Basel, Switzerland) ; Switzerland

2021

Abstract: Triangularia mangenotti was analyzed for the production of secondary metabolites, resulting in the isolation of known zopfinol (1) and its new derivatives zopfinol B-C (2-4), the 10-membered lactones 7-O-acetylmultiplolide A (5) and 8-O- ... ...

Abstract	Triangularia mangenotti was analyzed for the production of secondary metabolites, resulting in the isolation of known zopfinol (1) and its new derivatives zopfinol B-C (2-4), the 10-membered lactones 7-O-acetylmultiplolide A (5) and 8-O-acetylmultiplolide A (6), together with sordarin (7), sordarin B (8), and hypoxysordarin (9). The absolute configuration of 1 was elucidated by the synthesis of MPTA-esters. Compound 1 showed antimicrobial activity against the Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus and the fungus Mucor hiemalis. While 4 was weakly antibacterial, 3 showed stronger antibiotic activity against the Gram-positive bacteria and weak antifungal activity against M. hiemalis and Rhodotorula glutinis. We furthermore observed the cytotoxicity of 1, 3 and 4 against the mammalian cell lines KB3.1 and L929. Moreover, the new genus Pseudorhypophila is introduced herein to accommodate Triangularia mangenotii together with several species of Zopfiella-Z. marina, Z. pilifera, and Z. submersa. These taxa formed a well-supported monophyletic clade in the recently introduced family Navicularisporaceae, located far from the type species of the respective original genera, in a phylogram based on the combined dataset sequences of the internal transcribed spacer region (ITS), the nuclear rDNA large subunit (LSU), and fragments of the ribosomal polymerase II subunit 2 (rpb2) and β-tubulin (tub2) genes. Zopfiella submersa is synonymized with P. marina due to the phylogenetic and morphological similarity. The isolation of zopfinols 1-4 and sordarins 7-9 confirms the potential of this fungal order as producers of bioactive compounds and suggests these compounds as potential chemotaxonomic markers.
Keywords	Antimicrobials ; Naviculisporaceae ; Sordariales ; cytotoxicity ; secondary metabolites ; sordarins
Subject code	590
Language	English
Publishing date	2021-03-03
Publisher	MDPI
Publishing country	de
Document type	Article ; Online
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Article ; Online: Dissecting Herpes Simplex Virus 1-Induced Host Shutoff at the RNA Level.

Friedel, Caroline C / Whisnant, Adam W / Djakovic, Lara / Rutkowski, Andrzej J / Friedl, Marie-Sophie / Kluge, Michael / Williamson, James C / Sai, Somesh / Vidal, Ramon Oliveira / Sauer, Sascha / Hennig, Thomas / Grothey, Arnhild / Milić, Andrea / Prusty, Bhupesh K / Lehner, Paul J / Matheson, Nicholas J / Erhard, Florian / Dölken, Lars

Journal of virology

2021 Volume 95, Issue 3

Abstract: Herpes simplex virus 1 (HSV-1) induces a profound host shutoff during lytic infection. The virion host shutoff ( ...

Abstract	Herpes simplex virus 1 (HSV-1) induces a profound host shutoff during lytic infection. The virion host shutoff (
MeSH term(s)	Fibroblasts/metabolism ; Fibroblasts/virology ; Gene Expression Regulation, Viral ; Herpes Simplex/genetics ; Herpes Simplex/metabolism ; Herpes Simplex/pathology ; Herpes Simplex/virology ; Herpesvirus 1, Human/physiology ; Humans ; Protein Biosynthesis ; Proteome ; RNA, Viral/genetics ; RNA, Viral/metabolism ; Ribonucleases/genetics ; Ribonucleases/metabolism ; Transcriptome ; Viral Proteins/genetics ; Viral Proteins/metabolism ; Virus Replication
Chemical Substances	Proteome ; RNA, Viral ; Viral Proteins ; virion host shutoff protein, Simplexvirus (118367-50-3) ; Ribonucleases (EC 3.1.-)
Language	English
Publishing date	2021-01-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.01399-20
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Article ; Online: Dissecting Herpes Simplex Virus 1-Induced Host Shutoff at the RNA Level.

Journal of virology ; United States

2020

Abstract: Herpes simplex virus 1 (HSV-1) induces a profound host shut-off during lytic infection. The virion host shut-off (vhs) protein plays a key role in this process by efficiently cleaving host and viral mRNAs. Furthermore, the onset of viral DNA replication ... ...

Abstract	Herpes simplex virus 1 (HSV-1) induces a profound host shut-off during lytic infection. The virion host shut-off (vhs) protein plays a key role in this process by efficiently cleaving host and viral mRNAs. Furthermore, the onset of viral DNA replication is accompanied by a rapid decline in host transcriptional activity. To dissect relative contributions of both mechanisms and elucidate gene-specific host transcriptional responses throughout the first 8h of lytic HSV-1 infection, we employed RNA-seq of total, newly transcribed (4sU-labelled) and chromatin-associated RNA in wild-type (WT) and Δvhs infection of primary human fibroblasts. Following virus entry, vhs activity rapidly plateaued at an elimination rate of around 30% of cellular mRNAs per hour until 8h p.i. In parallel, host transcriptional activity dropped to 10-20%. While the combined effects of both phenomena dominated infection-induced changes in total RNA, extensive gene-specific transcriptional regulation was observable in chromatin-associated RNA and was surprisingly concordant between WT and Δvhs infection. Both induced strong transcriptional up-regulation of a small subset of genes that were poorly expressed prior to infection but already primed by H3K4me3 histone marks at their promoters. Most interestingly, analysis of chromatin-associated RNA revealed vhs-nuclease-activity-dependent transcriptional down-regulation of at least 150 cellular genes, in particular of many integrin adhesome and extracellular matrix components. This was accompanied by a vhs-dependent reduction in protein levels by 8h p.i. for many of these genes. In summary, our study provides a comprehensive picture of the molecular mechanisms that govern cellular RNA metabolism during the first 8h of lytic HSV-1 infection.IMPORTANCE The HSV-1 virion host shut-off (vhs) protein efficiently cleaves both host and viral mRNAs in a translation-dependent manner. In this study, we model and quantify changes in vhs activity as well as virus-induced global loss of host transcriptional activity during productive HSV-1 infection. In general, HSV-1-induced alterations in total RNA levels were dominated by these two global effects. In contrast, chromatin-associated RNA depicted gene-specific transcriptional changes. This revealed highly concordant transcriptional changes in WT and Δvhs infection, confirmed DUX4 as a key transcriptional regulator in HSV-1 infection and depicted vhs-dependent, transcriptional down-regulation of the integrin adhesome and extracellular matrix components. The latter explained seemingly gene-specific effects previously attributed to vhs-mediated mRNA degradation and resulted in a concordant loss in protein levels by 8h p.i. for many of the respective genes.
Subject code	570 ; 572
Language	English
Publishing date	2020-11-04
Publisher	American Society for Microbilogy (ASM)
Publishing country	de
Document type	Article ; Online
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Article: Reperfusion of pulmonary arteriovenous malformations after embolotherapy.

Milic, Andrea / Chan, Raymond P / Cohen, Justine H / Faughnan, Marie E

Journal of vascular and interventional radiology : JVIR

2005 Volume 16, Issue 12, Page(s) 1675–1683

Abstract: Purpose: To describe the mechanisms and risk factors associated with reperfusion of successfully treated pulmonary arteriovenous malformations (PAVMs) after embolotherapy.: Materials and methods: Among 112 consecutive patients with PAVMs treated by ... ...

Abstract	Purpose: To describe the mechanisms and risk factors associated with reperfusion of successfully treated pulmonary arteriovenous malformations (PAVMs) after embolotherapy. Materials and methods: Among 112 consecutive patients with PAVMs treated by embolotherapy, 19 patients were identified who had 33 angiographically confirmed reperfused PAVMs. A retrospective analysis of computed tomography (CT) and angiography was performed in patients with documented reperfused PAVMs in which reperfused PAVMs were compared with nonreperfused PAVMs. CT images were examined for persistence of the aneurysm and/or draining vein after initial embolotherapy and correlated with angiography to determine the mechanism of reperfusion. PAVM and embolic agent characteristics (eg, feeding artery size and number; PAVM location; coil size, number, and location) were evaluated for association with reperfusion. The outcomes of repeat embolotherapy for reperfused PAVMs were evaluated. Results: The PAVM aneurysm and/or draining vein persisted on CT after initial embolotherapy in all reperfused PAVMs and resolved in all nonreperfused PAVMs (in patients with nondiffuse PAVMs). Recanalization was the mechanism of reperfusion in 88%. Reperfusion was associated with the use of a single coil (P < .0001), oversized coils (P < .0001), coil placement more than 1 cm from the aneurysm (P < .0001), and increased feeding artery size (P < .001). Repeat embolotherapy for reperfused PAVMs was technically successful in 94% of cases. In the remaining 6% of cases, insufficient feeding artery length prevented safe repeat treatment. After a mean follow-up of 41 months, 42% of reperfused PAVMs in our series have been successfully treated again and occluded. Conclusions: Recanalization is the most common mechanism of PAVM reperfusion. Increased feeding artery diameter, low number of coils, use of oversized coils, and proximal coil placement within the feeding artery are associated with reperfusion. Distal coil placement facilitates repeat embolization if reperfusion occurs.
MeSH term(s)	Adult ; Aneurysm/diagnostic imaging ; Aneurysm/therapy ; Arteriovenous Malformations/diagnostic imaging ; Arteriovenous Malformations/therapy ; Embolization, Therapeutic/instrumentation ; Embolization, Therapeutic/methods ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Pulmonary Artery/abnormalities ; Pulmonary Artery/diagnostic imaging ; Radiography, Interventional ; Reperfusion/instrumentation ; Reperfusion/methods ; Retreatment ; Retrospective Studies ; Risk Factors ; Tomography, X-Ray Computed ; Treatment Outcome ; Vascular Patency
Language	English
Publishing date	2005-12
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1137756-2
ISSN	1535-7732 ; 1051-0443
ISSN (online)	1535-7732
ISSN	1051-0443
DOI	10.1097/01.RVI.0000182163.25493.BB
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Article: Laparoscopic ultrasound-guided radiofrequency ablation of uterine fibroids.

Milic, Andrea / Asch, Murray R / Hawrylyshyn, Peter A / Allen, Lisa M / Colgan, Terence J / Kachura, John R / Hayeems, Eran B

Cardiovascular and interventional radiology

2006 Volume 29, Issue 4, Page(s) 694–698

Abstract: Four patients with symptomatic uterine fibroids measuring less than 6 cm underwent laparoscopic ultrasound-guided radiofrequency ablation (RFA) using multiprobe-array electrodes. Follow-up of the treated fibroids was performed with gadolinium-enhanced ... ...

Abstract	Four patients with symptomatic uterine fibroids measuring less than 6 cm underwent laparoscopic ultrasound-guided radiofrequency ablation (RFA) using multiprobe-array electrodes. Follow-up of the treated fibroids was performed with gadolinium-enhanced magnetic resonance imaging (MRI) and patients' symptoms were assessed by telephone interviews. The procedure was initially technically successful in 3 of the 4 patients and MRI studies at 1 month demonstrated complete fibroid ablation. Symptom improvement, including a decrease in menstrual bleeding and pain, was achieved in 2 patients at 3 months. At 7 months, 1 of these 2 patients experienced symptom worsening which correlated with recurrent fibroid on MRI. The third, initially technically successfully treated patient did not experience any symptom relief after the procedure and was ultimately diagnosed with adenomyosis. Our preliminary results suggest that RFA is a technically feasible treatment for symptomatic uterine fibroids in appropriately selected patients.
MeSH term(s)	Adult ; Catheter Ablation/methods ; Female ; Humans ; Laparoscopy ; Leiomyoma/diagnostic imaging ; Leiomyoma/surgery ; Leiomyoma/therapy ; Middle Aged ; Ultrasonography ; Uterine Neoplasms/diagnostic imaging ; Uterine Neoplasms/surgery ; Uterine Neoplasms/therapy
Language	English
Publishing date	2006-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603082-8
ISSN	1432-086X ; 0174-1551 ; 0342-7196
ISSN (online)	1432-086X
ISSN	0174-1551 ; 0342-7196
DOI	10.1007/s00270-005-0045-9
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Article: Prenatal detection of microtia by MRI in a fetus with trisomy 22.

Milic, Andrea / Blaser, Susan / Robinson, Ashley / Viero, Sandra / Halliday, William / Winsor, Elizabeth / Toi, Ants / Thomas, Micki / Chitayat, David

Pediatric radiology

2006 Volume 36, Issue 7, Page(s) 706–710

Abstract: Trisomy 22 is a rare chromosomal abnormality infrequently detected prenatally. External ear abnormalities, in particular microtia, are often associated with trisomy 22, but prenatal detection of microtia has not been reported in association with trisomy ... ...

Abstract	Trisomy 22 is a rare chromosomal abnormality infrequently detected prenatally. External ear abnormalities, in particular microtia, are often associated with trisomy 22, but prenatal detection of microtia has not been reported in association with trisomy 22. We report a fetus with trisomy 22, with fetal MRI findings of microtia, craniofacial dysmorphism, and polygyria. Fetal MRI is a useful tool for auricular assessment and might have utility in the prenatal detection of chromosomal abnormalities, especially among fetuses with structural anomalies.
MeSH term(s)	Autopsy ; Chromosomes, Human, Pair 22 ; Ear, External/abnormalities ; Female ; Humans ; Magnetic Resonance Imaging/methods ; Pregnancy ; Prenatal Diagnosis ; Trisomy/diagnosis
Language	English
Publishing date	2006-07
Publishing country	Germany
Document type	Case Reports ; Journal Article
ZDB-ID	124459-0
ISSN	1432-1998 ; 0301-0449
ISSN (online)	1432-1998
ISSN	0301-0449
DOI	10.1007/s00247-006-0155-9
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Article: Altered p27(Kip1) phosphorylation, localization, and function in human epithelial cells resistant to transforming growth factor beta-mediated G(1) arrest.

Ciarallo, Sandra / Subramaniam, Venkateswaran / Hung, Wesley / Lee, Jin-Hwa / Kotchetkov, Rouslan / Sandhu, Charanjit / Milic, Andrea / Slingerland, Joyce M

Molecular and cellular biology

2002 Volume 22, Issue 9, Page(s) 2993–3002

Abstract: p27(Kip1) is an important effector of G(1) arrest by transforming growth factor beta (TGF-beta). Investigations in a human mammary epithelial cell (HMEC) model, including cells that are sensitive (184(S)) and resistant (184A1L5(R)) to G(1) arrest by TGF- ... ...

Abstract	p27(Kip1) is an important effector of G(1) arrest by transforming growth factor beta (TGF-beta). Investigations in a human mammary epithelial cell (HMEC) model, including cells that are sensitive (184(S)) and resistant (184A1L5(R)) to G(1) arrest by TGF-beta, revealed aberrant p27 regulation in the resistant cells. Cyclin E1-cyclin-dependent kinase 2 (cdk2) and cyclin A-cdk2 activities were increased, and p27-associated kinase activity was detected in 184A1L5(R) cells. p27 from 184A1L5(R) cells was localized to both nucleus and cytoplasm, showed an altered profile of phosphoisoforms, and had a reduced ability to bind and inhibit cyclin E1-cdk2 in vitro when compared to p27 from the sensitive 184(S) cells. In proliferating 184A1L5(R) cells, more p27 was associated with cyclin D1-cdk4 complexes than in 184(S). While TGF-beta inhibited the formation of cyclin D1-cdk4-p27 complexes in 184(S) cells, it did not inhibit the assembly of cyclin D1-cdk4-p27 complexes in the resistant 184A1L5(R) cells. p27 phosphorylation changed during cell cycle progression, with cyclin E1-bound p27 in G(0) showing a different phosphorylation pattern from that of cyclin D1-bound p27 in mid-G(1). These data suggest a model in which TGF-beta modulates p27 phosphorylation from its cyclin D1-bound assembly phosphoform to an alternate form that binds tightly to inhibit cyclin E1-cdk2. Altered phosphorylation of p27 in the resistant 184A1L5(R) cells may favor the binding of p27 to cyclin D1-cdk4 and prevent its accumulation in cyclin E1-cdk2 in response to TGF-beta.
MeSH term(s)	Cell Cycle Proteins/metabolism ; Checkpoint Kinase 2 ; Cyclin D1/metabolism ; Cyclin E/metabolism ; Cyclin-Dependent Kinase Inhibitor p27 ; Epithelial Cells/drug effects ; Epithelial Cells/metabolism ; Flow Cytometry ; G1 Phase/drug effects ; Humans ; Immunohistochemistry ; Isoelectric Focusing ; Macromolecular Substances ; Phosphorylation ; Protein Binding ; Protein Kinases/metabolism ; Protein Serine-Threonine Kinases ; Temperature ; Transforming Growth Factor beta/pharmacology ; Tumor Cells, Cultured ; Tumor Suppressor Proteins/metabolism
Chemical Substances	Cell Cycle Proteins ; Cyclin E ; Macromolecular Substances ; Transforming Growth Factor beta ; Tumor Suppressor Proteins ; Cyclin D1 (136601-57-5) ; Cyclin-Dependent Kinase Inhibitor p27 (147604-94-2) ; Protein Kinases (EC 2.7.-) ; Checkpoint Kinase 2 (EC 2.7.1.11) ; CHEK2 protein, human (EC 2.7.11.1) ; Protein Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2002-03-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	779397-2
ISSN	1098-5549 ; 0270-7306
ISSN (online)	1098-5549
ISSN	0270-7306
DOI	10.1128/MCB.22.9.2993-3002.2002
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