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- Hein, Kyaw Zaw, et al.
(författare)
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Disulphide-reduced psoriasin is a human apoptosis-inducing broad-spectrum fungicide.
- 2015
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 112:42, s. 13039-44
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Tidskriftsartikel (refereegranskat)abstract
- The unexpected resistance of psoriasis lesions to fungal infections suggests local production of an antifungal factor. We purified Trichophyton rubrum-inhibiting activity from lesional psoriasis scale extracts and identified the Cys-reduced form of S100A7/psoriasin (redS100A7) as a principal antifungal factor. redS100A7 inhibits various filamentous fungi, including the mold Aspergillus fumigatus, but not Candida albicans. Antifungal activity was inhibited by Zn(2+), suggesting that redS100A7 interferes with fungal zinc homeostasis. Because S100A7-mutants lacking a single cysteine are no longer antifungals, we hypothesized that redS100A7 is acting as a Zn(2+)-chelator. Immunogold electron microscopy studies revealed that it penetrates fungal cells, implicating possible intracellular actions. In support with our hypothesis, the cell-penetrating Zn(2+)-chelator TPEN was found to function as a broad-spectrum antifungal. Ultrastructural analyses of redS100A7-treated T. rubrum revealed marked signs of apoptosis, suggesting that its mode of action is induction of programmed cell death. TUNEL, SYTOX-green analyses, and caspase-inhibition studies supported this for both T. rubrum and A. fumigatus. Whereas redS100A7 can be generated from oxidized S100A7 by action of thioredoxin or glutathione, elevated redS100A7 levels in fungal skin infection indicate induction of both S100A7 and its reducing agent in vivo. To investigate whether redS100A7 and TPEN are antifungals in vivo, we used a guinea pig tinea pedes model for fungal skin infections and a lethal mouse Aspergillus infection model for lung infection and found antifungal activity in both in vivo animal systems. Thus, selective fungal cell-penetrating Zn(2+)-chelators could be useful as an urgently needed novel antifungal therapeutic, which induces programmed cell death in numerous fungi.
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| 2. |
- Rakhlin, Natalia, et al.
(författare)
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Language development of internationally adopted children : Adverse early experiences outweigh the age of acquisition effect
- 2015
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Ingår i: Journal of Communication Disorders. - : Elsevier BV. - 0021-9924 .- 1873-7994. ; 57:SI, s. 66-80
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Tidskriftsartikel (refereegranskat)abstract
- We compared English language and cognitive skills between internationally adopted children (IA; mean age at adoption=2.24, SD=1.8) and their non-adopted peers from the US reared in biological families (BF) at two time points. We also examined the relationships between outcome measures and age at initial institutionalization, length of institutionalization, and age at adoption. On measures of general language, early literacy, and non-verbal IQ, the IA group performed significantly below their age-peers reared in biological families at both time points, but the group differences disappeared on receptive vocabulary and kindergarten concept knowledge at the second time point. Furthermore, the majority of children reached normative age expectations between 1 and 2 years post-adoption on all standardized measures. Although the age at adoption, age of institutionalization, length of institutionalization, and time in the adoptive family all demonstrated significant correlations with one or more outcome measures, the negative relationship between length of institutionalization and child outcomes remained most robust after controlling for the other variables. Results point to much flexibility and resilience in children's capacity for language acquisition as well as the potential primacy of length of institutionalization in explaining individual variation in IA children's outcomes.LEARNING OUTCOMES: (1) Readers will be able to understand the importance of pre-adoption environment on language and early literacy development in internationally adopted children. (2) Readers will be able to compare the strength of the association between the length of institutionalization and language outcomes with the strength of the association between the latter and the age at adoption. (3) Readers will be able to understand that internationally adopted children are able to reach age expectations on expressive and receptive language measures despite adverse early experiences and a replacement of their first language with an adoptive language.
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