| 1. |
- Björkman, G., et al.
(författare)
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Att genomföra och avrapportera projektarbetsuppgifter på delkurs PK:1
- 1977
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Detta är en rapport om hur man bedriver och avrapporterar projektarbete på kurs PK:1 i informationsbehandling. Rapporten beskriver de olika momenten i projektarbetet och innehåller dessutom regler och anvisningar för detta arbete. Rapporten försöker även förmedla tips och erfarenheter från tidigare terminer beträffande kurs PK:1
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| 2. |
- Pasupuleti, Mukesh, et al.
(författare)
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Antimicrobial activity of human prion protein is mediated by its N-terminal region
- 2009
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 4:10, s. e7358-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cellular prion-related protein (PrP(c)) is a cell-surface protein that is ubiquitously expressed in the human body. The multifunctionality of PrP(c), and presence of an exposed cationic and heparin-binding N-terminus, a feature characterizing many antimicrobial peptides, made us hypothesize that PrP(c) could exert antimicrobial activity. METHODOLOGY AND PRINCIPAL FINDINGS: Intact recombinant PrP exerted antibacterial and antifungal effects at normal and low pH. Studies employing recombinant PrP and N- and C-terminally truncated variants, as well as overlapping peptide 20mers, demonstrated that the antimicrobial activity is mediated by the unstructured N-terminal part of the protein. Synthetic peptides of the N-terminus of PrP killed the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, and the Gram-positive Bacillus subtilis and Staphylococcus aureus, as well as the fungus Candida parapsilosis. Fluorescence studies of peptide-treated bacteria, paired with analysis of peptide effects on liposomes, showed that the peptides exerted membrane-breaking effects similar to those seen after treatment with the "classical" human antimicrobial peptide LL-37. In contrast to LL-37, however, no marked helix induction was detected for the PrP-derived peptides in presence of negatively charged (bacteria-mimicking) liposomes. PrP furthermore showed an inducible expression during wounding of human skin ex vivo and in vivo, as well as stimulation of keratinocytes with TGF-alpha in vitro. CONCLUSIONS: The demonstration of an antimicrobial activity of PrP, localisation of its activity to the N-terminal and heparin-binding region, combined with results showing an increased expression of PrP during wounding, indicate that PrPs could have a previously undisclosed role in host defense.
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| 3. |
- Roupé, Karl Markus, et al.
(författare)
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Transcription Factor Binding Site Analysis Identifies FOXO Transcription Factors as Regulators of the Cutaneous Wound Healing Process.
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:2
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Tidskriftsartikel (refereegranskat)abstract
- The search for significantly overrepresented and co-occurring transcription factor binding sites in the promoter regions of the most differentially expressed genes in microarray data sets could be a powerful approach for finding key regulators of complex biological processes. To test this concept, two previously published independent data sets on wounded human epidermis were re-analyzed. The presence of co-occurring transcription factor binding sites for FOXO1, FOXO3 and FOXO4 in the majority of the promoter regions of the most significantly differentially expressed genes between non-wounded and wounded epidermis implied an important role for FOXO transcription factors during wound healing. Expression levels of FOXO transcription factors during wound healing in vivo in both human and mouse skin were analyzed and a decrease for all FOXOs in human wounded skin was observed, with FOXO3 having the highest expression level in non wounded skin. Impaired re-epithelialization was found in cultures of primary human keratinocytes expressing a constitutively active variant of FOXO3. Conversely knockdown of FOXO3 in keratinocytes had the opposite effect and in an in vivo mouse model with FOXO3 knockout mice we detected significantly accelerated wound healing. This article illustrates that the proposed approach is a viable method for identifying important regulators of complex biological processes using in vivo samples. FOXO3 has not previously been implicated as an important regulator of wound healing and its exact function in this process calls for further investigation.
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| 4. |
- Roupé, Markus, et al.
(författare)
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Gene expression demonstrates increased resilience toward harmful inflammatory stimuli in the proliferating epidermis of human skin wounds
- 2010
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Ingår i: Experimental Dermatology. - : Wiley. - 0906-6705 .- 1600-0625. ; 19:8, s. 329-332
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Tidskriftsartikel (refereegranskat)abstract
- We examined the epidermal gene expression during the proliferative phase of wound healing. Matrix metalloproteases were the group of proteases most prominently up-regulated in skin wounds, whereas serine protease inhibitors were the most strongly up-regulated protease inhibitors. Furthermore, we found down-regulation of genes involved in the extrinsic pathway of apoptosis. This together with the up-regulation of inhibitors of leukocyte serine proteases likely represents a protective step to ensure survival of keratinocytes in the inflammatory wound environment. The down-regulation of proapoptotic genes in the extrinsic pathway of apoptosis was not accompanied by a down-regulation of receptors indicating that the keratinocytes in skin wounds did not become less responsive to external stimuli. Examining the transcription factor binding sites in the promoters of the most differentially expressed genes between normal skin and skin wounds a significant overrepresentation of binding sites were found for STAT-5, SRY and members of the FOXO-family of transcription factors.
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| 5. |
- Roupé, Markus, et al.
(författare)
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Injury Is a Major Inducer of Epidermal Innate Immune Responses during Wound Healing.
- 2010
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Ingår i: Journal of Investigative Dermatology. - : Elsevier BV. - 1523-1747 .- 0022-202X. ; 130, s. 1167-1177
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Tidskriftsartikel (refereegranskat)abstract
- We examined the importance of injury for the epidermal innate immune response in human skin wounds. We found that injury, independent of infiltrating inflammatory cells, generated prominent chemotactic activity toward neutrophils in injured skin because of IL-8 production. Furthermore, injury was a major inducer of the expression of antimicrobial (poly)peptides (AMPs) in skin wounds. In human skin, these injury-induced innate immune responses were mediated by activation of the epidermal growth factor receptor (EGFR). Consequently, inhibition of the EGFR blocked both the chemotactic activity generated in injured skin and the expression of the majority of the AMPs. The importance of injury was confirmed in mouse experiments in vivo, in which injury independent of infection was a potent inducer of AMPs in skin wounds. To our knowledge, these data thereby provide a previously unreported molecular link between injury and neutrophil accumulation and identify the molecular background for the vast expression of IL-8 and AMPs in wounded epidermis. Conceptually, these data show that the growth factor response elicited by injury is important for the recruitment of neutrophils in skin wounds.Journal of Investigative Dermatology advance online publication, 3 September 2009; doi:10.1038/jid.2009.284.
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