Exposed CendR Domain in Homing Peptide Yields Skin-Targeted Therapeutic in Epidermolysis Bullosa

Systemic skin-selective therapeutics would be a major advancement in the treatment of diseases affecting the entire skin, such as recessive dystrophic epidermolysis bullosa (RDEB), which is caused by mutations in the COL7A1 gene and manifests in transforming growth factor-beta (TGF-beta)-driven fibrosis and malignant transformation. Homing peptides containing a C-terminal R/KXXR/K motif (C-end rule [CendR] sequence) activate an extravasation and tissue penetration pathway for tumor-specific drug delivery. We have previously described a homing peptide CRKDKC (CRK) that contains a cryptic CendR motif and homes to angiogenic blood vessels in wounds and tumors, but it cannot penetrate cells or tissues. In this study, we demonstrate that removal of the cysteine from CRK to expose the CendR sequence confers the peptide novel ability to home to normal skin. Fusion of the truncated CRK (tCRK) peptide to the C terminus of an extracellular matrix protein de-corin (DCN), a natural TGF-beta inhibitor, resulted in a skin-homing therapeutic molecule (DCN-tCRK). Systemic DCN-tCRK administration in RDEB mice led to inhibition of TGF-beta signaling in the skin and significant improvement in the survival of RDEB mice. These results suggest that DCN-tCRK has the potential to be utilized as a novel therapeutic compound for the treatment of dermatological diseases such as RDEB.Peer reviewe

Responses of silver birch rhizosphere to long-term CO2 and O3 exposure

vo

Mycorrhizas and host plant chemical defence as a potential controlling agent for incect herbivore damages on scots pine

vo

Decomposition and feeding experiments with leaf litter of silver birches grown under elevated CO2- and O3-levels

vokmk

Öndunar kúlur - Dynamisk installasjon for bærekraftig luftkvalitet

Dette prosjektet har røtter fra forarbeidet «Kunnskap om luftkvalitet i Gjøvik» som omhandler samme tema. Prosjektet vårt bygger på kunnskapen om at det er informasjonsmangel om luftkvalitet blant innbyggerne i Gjøvik. Denne kunnskapen benytter vi for å lage en installasjon som dekker behovet for informasjon. Vi tar for oss ulike teorier om adferdsendring, og drøfter effekten av bærekraft på prosjektet. Under forarbeidet hadde vi utformet innsikten, og dette ble benyttet under prosjektet til å utvikle et konsept. Vi anvendte designemetodikk for å utforske og idémyldre ulike konsepter før vi landet på Öndunar kúlur. Dette konseptet ble prototypet både digitalt og fysisk, der begge versjonene ble brukertestet. Resultatet ble konseptet og prototypen til den. Konseptet går ut på å informere om luftkvalitet gjennom en dynamisk lysinstallasjon, samt motivere gjennom en Mjøs-konkurranse, og fasilitere for nye vaner gjennom et digitalt aspekt. Öndunar kúlur er altså en installasjon bestående av to kuler som formidler luftkvaliteten nå, og varsel for i morgen, samt tre benker som representerer de tre Mjøsbyene Gjøvik, Hamar og Lillehammer.This project is based on the groundwork done in the preliminary work «Kunnskap om luftkvalitet i Gjøvik» which concerns the same topic. Our project is built on the knowledge that there is a lack of information regarding air quality among the citizens of Gjøvik. We will use this knowledge to create an installation to satisfy this need for information. We assess theories about behavioral change, and discuss the effects of sustainability on the project. The insight was developed during the preliminary work, and was used during the project to develop a concept. We utilized design methodology to explore and brainstorm different concept before we landed on Öndunar kúlur. This concept was prototyped digitally and physically, and both versions were user tested. The result was a consept with an accompanying prototype. The concept involves informing about air quality through a dynamic light installation, as well as motivating through a Mjøs competition, and fasilitate for new habits through a digital aspect. Ödunar kúlur is an installation consisting of two spheres individually conveying the air quality now, and for tomorrow. In addition three benches representing the three Mjøs cities Gjøvik, Hamar and Lillehammer

Öndunar kúlur - Dynamisk installasjon for bærekraftig luftkvalitet

Dette prosjektet har røtter fra forarbeidet «Kunnskap om luftkvalitet i Gjøvik» som omhandler samme tema. Prosjektet vårt bygger på kunnskapen om at det er informasjonsmangel om luftkvalitet blant innbyggerne i Gjøvik. Denne kunnskapen benytter vi for å lage en installasjon som dekker behovet for informasjon. Vi tar for oss ulike teorier om adferdsendring, og drøfter effekten av bærekraft på prosjektet. Under forarbeidet hadde vi utformet innsikten, og dette ble benyttet under prosjektet til å utvikle et konsept. Vi anvendte designemetodikk for å utforske og idémyldre ulike konsepter før vi landet på Öndunar kúlur. Dette konseptet ble prototypet både digitalt og fysisk, der begge versjonene ble brukertestet. Resultatet ble konseptet og prototypen til den. Konseptet går ut på å informere om luftkvalitet gjennom en dynamisk lysinstallasjon, samt motivere gjennom en Mjøs-konkurranse, og fasilitere for nye vaner gjennom et digitalt aspekt. Öndunar kúlur er altså en installasjon bestående av to kuler som formidler luftkvaliteten nå, og varsel for i morgen, samt tre benker som representerer de tre Mjøsbyene Gjøvik, Hamar og Lillehammer

Carbonic Anhydrase VI in Skin Wound Healing Study on Car6Knockout Mice

Carbonic anhydrases (CAs) contribute to tumor cell migration by generating an acidic environment through the conversion of carbon dioxide to bicarbonate and a proton. CA VI is secreted to milk and saliva, and it could contribute to wound closure, as a potential trophic factor, in animals that typically lick their wounds. Our aim was to investigate whether human CA VI improves skin-wound healing in full-thickness skin-wound models. The effect was studied in Car6 −/− knockout mice and wild type littermates. Half of both mice strains were given topically administered, milk-derived CA VI after wounding and eight hours later. The amount of topically given CA VI exceeded the predicted amount of natural saliva-delivered CA VI. The healing was followed for seven days and studied from photographs and histological sections. Our results showed no significant differences between the treatment groups in wound closure, re-epithelization, or granulation tissue formation, nor did the Car6 genotype affect the healing. Our results demonstrate that CA VI does not play a major role in skin-wound healing and also suggest that saliva-derived CA VI is not responsible for the licking-associated improved wound healing in animals

Carbonic Anhydrase VI in Skin Wound Healing Study on Car6 Knockout Mice

Carbonic anhydrases (CAs) contribute to tumor cell migration by generating an acidic environment through the conversion of carbon dioxide to bicarbonate and a proton. CA VI is secreted to milk and saliva, and it could contribute to wound closure, as a potential trophic factor, in animals that typically lick their wounds. Our aim was to investigate whether human CA VI improves skin-wound healing in full-thickness skin-wound models. The effect was studied in Car6 −/− knockout mice and wild type littermates. Half of both mice strains were given topically administered, milk-derived CA VI after wounding and eight hours later. The amount of topically given CA VI exceeded the predicted amount of natural saliva-delivered CA VI. The healing was followed for seven days and studied from photographs and histological sections. Our results showed no significant differences between the treatment groups in wound closure, re-epithelization, or granulation tissue formation, nor did the Car6 genotype affect the healing. Our results demonstrate that CA VI does not play a major role in skin-wound healing and also suggest that saliva-derived CA VI is not responsible for the licking-associated improved wound healing in animals.</jats:p