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- Andersson, Emma, 1978-
(författare)
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Human adenoviruses : new bioassays for antiviral screening and CD46 interaction
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Adenoviruses are common pathogens all over the world. The majority of the population has at some point been infected with an adenovirus. Although severe disease can occur in otherwise healthy individuals an adenovirus infection is most commonly self limited in these cases. For immunocompromised individuals however, adenoviruses can be life-threatening pathogens capable of causing disseminated disease and multiple organ failure. Still there is no approved drug specific for treatment of adenovirus infections. We have addressed this using a unique whole cell viral replication reporter gene assay to screen small organic molecules for anti-adenoviral effect. This RCAd11pGFP-vector based assay allowed screening without any preconceived idea of the mechanism for adenovirus inhibition. As a result of the screening campaign 2-[[2-(benzoylamino)benzoyl]amino]-benzoic acid turned out to be a potent inhibitor of adenoviral replication. To establish a structure-activity relationship a number of analogs were synthesized and evaluated for their anti-adenoviral effect. The carboxylic acid moiety of the molecule was important for efficient inhibition of adenovirus replication.There are 54 adenovirus types characterized today and these are divided into seven species, A-G. The receptors used by species B and other adenoviruses are not fully characterized. CD46 is a complement regulatory molecule suggested to be used by all species B types and some species D types but this is not established. We have designed a new bioassay for assessment of the interaction between adenoviruses and CD46 and investigated the CD46-binding capacity of adenovirus types indicated to interact with CD46. We concluded that Ad11p, Ad34, Ad35, and Ad50 clearly bind CD46 specifically, whereas Ad3p, Ad7p, Ad14, and Ad37 do not.CD46 is expressed on all human nucleated cells and serves as a receptor for a number of different bacteria and viruses. Downregulation of CD46 on the cell surface occurs upon binding by some of these pathogens. We show that early in infection Ad11p virions downregulate CD46 upon binding to a much higher extent than the complement regulatory molecules CD55 and CD59.These findings may lead to a better understanding of the pathogenesis of adenoviruses in general and species B adenoviruses in particular and hopefully we have discovered a molecule that can be the basis for development of new anti-adenoviral drugs.
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| 2. |
- Cataldi, Gianni, 1986-
(författare)
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Debris disks from an astronomical and an astrobiological viewpoint
- 2013
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this licentiate thesis, I consider debris disks from an observational, astronomical viewpoint, but also discuss a potential astrobiological application. Debris disks are essentially disks of dust and rocks around main-sequence stars, analogue to the Kuiper- or the asteroid belt in our solar system. Their observation and theoretical modeling can help to constrain planet formation models and help in the understanding of the history of the solar system. After a general introduction into the field of debris disks and some basic debris disk physics, the thesis concentrates on the observation of gas in debris disks. The possible origins of this gas and its dynamics are discussed and it is considered what it can tell us about the physical conditions in the disk and possibly about the dust composition. In this way, the paper associated with this thesis (dealing with the gas in the β Pic debris disk) is set into context. More in detail, we observed the CII emission originating from the carbon-rich β Pic disk with Herschel HIFI and attempted to constrain the spatial distribution of the gas from the shape of the emission line. This is necessary since the gas production mechanism is currently unknown, but can be constraint by obtaining information about the spatial profile of the gas. The last part of the thesis describes our preliminary studies of the possibility of a debris disk containing biomarkers, created by a giant impact on a life-bearing exoplanet.
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