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

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

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

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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

Screening for ACTH-dependent hypercortisolism in patients affected with pituitary incidentaloma

Context: Pituitary incidentalomas (PIs) are commonly encountered in clinical practice. The management of these asymptomatic pituitary lesions is still controversial. Systematic screening for subclinical or mild ACTH-dependent hypercortisolism (AH) is not presently recommended, due to the limited data available thus far on the epidemiological and clinical relevance of this condition in patients with PIs. As subclinical hypercortisolism (SH) was considered to be associated with chronic complications of overt cortisol excess, such as hypertension, diabetes, and osteoporosis, this disorder should be diagnosed at the early stage. Objective: The objective of this study was to evaluate the prevalence of hypercortisolism in a population of subjects with PIs. Design, subjects, and methods: A total of 68 consecutive patients (48 females and 20 males, aged 18-82 years) without clinically overt hypercortisolism, who were referred for evaluation of PIs between January 2010 and March 2013, were prospectively investigated for AH. Pituitary hypercortisolism was diagnosed in the presence of cortisol >50 nmol/l after 1 mg dexamethasone suppression test, non-suppressed ACTH, and the additional finding of one of the following: urinary free cortisol (UFC) >193 nmol/24 h, and midnight serum and salivary cortisol levels >207 and 2.8 nmol/l respectively. Results: Among patients with PIs, we found a 7.3% rate of pituitary hypercortisolism diagnosed with biochemical criteria and a 4.4% rate of histologically confirmed AH. Conclusions: Subclinical or mild hypercortisolism may be more common than generally perceived in patients with PIs

IL-13Rα1 Suppresses Tumor Progression in Two-stage Skin Carcinogenesis Model by Regulating Regulatory T Cells

Type 2-inflammation-related cytokine Interleukin (IL)-13 plays a protective role in experimental papilloma induction in mice. To understand mechanisms by which IL-13 contributes to papilloma formation we utilized IL-13Rα1 knockout (KO) mice in widely used DMBA/TPA two-stage skin carcinogenesis protocol that mimics the development of Squamous Cell Carcinoma (SCC). KO mice developed more papillomas and significantly faster than wild-type (WT) mice. Papilloma development reduced Tregs in WT mice, but substantially less in KO mice. In line with this, IL-2 and IL-10 levels decreased in WT mice, but not in KO mice. Furthermore, systemic IL-5 and Thymic Stromal Lymphopoietin (TSLP) levels were elevated, while IL-22 was decreased during papilloma formation in the skin of KO mice. Polymorphonuclear Myeloid-derived suppressor cells (PMN-MDSCs) were decreased in the KO mice at the early phase of papilloma induction. We demonstrate that IL-13Rα1 protects from papilloma development in chemically induced skin carcinogenesis and our results provide further insights into the protective role of functional IL-4 and IL-13 signaling via type II IL-4R in tumor development.publishedVersionPeer reviewe