| 1. |
- Björkgren, Mårten, et al.
(författare)
-
En komparativ förståelse av ämnesdidaktiska prepositioner
- 2019
-
Ingår i: Nordidactica. - Karlstad : CSD Karlstad. - 2000-9879. ; :2019:3, s. 45-72
-
Tidskriftsartikel (refereegranskat)abstract
- The national curricular guidelines for basic education and upper secondary school require teachers to have a readiness to teach and cooperate in accordance with a holistic multidisciplinary principle. The teacher education programmes in Finland are challenged to develop research-based knowledge about learning processes in holistic multidisciplinary teaching concerning both theory and practice. In this article, focus is put on comparisons between the subject-didactic perspectives of Art, Religion, History, and Social Studies. Referring to Lindström, the prepositions about, in, with and through are used as a point of departure for the aesthetic fields. The comparison is based on the prepositional perspective and particularly focusses on the understanding of the didactic emphases and ambitions. The subject-comparative reflection between similarities and differences is based on a socio-cultural view of learning, and the perspectives qualification, socialisation and subjectification by Giert Biesta. The article contributes to a consciousness about meaningful subject-didactic prerequisites for holistic multidisciplinary cooperation.
|
|
| 2. |
- Hanson, Britt, et al.
(författare)
-
Non-uniform dystrophin re-expression after CRISPR-mediated exon excision in the dystrophin/utrophin double-knockout mouse model of DMD
- 2022
-
Ingår i: Molecular Therapy Nucleic Acids. - : Elsevier. - 2162-2531. ; 30, s. 379-397
-
Tidskriftsartikel (refereegranskat)abstract
- Duchenne muscular dystrophy (DMD) is the most prevalent inherited myopathy affecting children, caused by genetic loss of the gene encoding the dystrophin protein. Here we have investigated the use of the Staphylococcus aureus CRISPR-Cas9 system and a double-cut strategy, delivered using a pair of adeno-associated virus serotype 9 (AAV9) vectors, for dystrophin restoration in the severely affected dystrophin/utrophin double-knockout (dKO) mouse. Single guide RNAs were designed to excise Dmd exon 23, with flanking intronic regions repaired by non-homologous end joining. Exon 23 deletion was confirmed at the DNA level by PCR and Sanger sequencing, and at the RNA level by RT-qPCR. Restoration of dystrophin protein expression was demonstrated by western blot and immunofluorescence staining in mice treated via either intraperitoneal or intravenous routes of delivery. Dystrophin restoration was most effective in the diaphragm, where a maximum of 5.7% of wild-type dystrophin expression was observed. CRISPR treatment was insufficient to extend lifespan in the dKO mouse, and dystrophin was expressed in a within-fiber patchy manner in skeletal muscle tissues. Further analysis revealed a plethora of non-productive DNA repair events, including AAV genome integration at the CRISPR cut sites. This study highlights potential challenges for the successful development of CRISPR therapies in the context of DMD.
|
|
| 3. |
- Johansson, Susanne M C, et al.
(författare)
-
Multivalent sialic acid conjugates inhibit adenovirus type 37 from binding to and infecting human corneal epithelial cells
- 2007
-
Ingår i: Antiviral Research. - : Elsevier BV. - 0166-3542 .- 1872-9096. ; 73:2, s. 92-100
-
Tidskriftsartikel (refereegranskat)abstract
- Adenovirus type 37 is one of the main causative agents of epidemic keratoconjunctivitis. In a series of publications, we have reported that this virus uses sialic acid as a cellular receptor. Here we demonstrate in vitro that on a molar basis, multivalent sialic acid conjugated to human serum albumin prevents adenovirus type 37 from binding to and infecting human corneal epithelial cells 1000-fold more efficiently than monosaccharidic sialic acid. We also demonstrate that the extraordinary inhibitory effect of multivalent sialic acid is due to the ability of this compound to aggregate virions. We conclude that multivalent sialic acid may be a potential new antiviral drug, for use in the treatment of epidemic keratoconjunctivitis caused by the adenoviruses that use sialic acid as cellular receptor.
|
|
| 4. |
- Sulniute, Rima, et al.
(författare)
-
Plasminogen is a critical regulator of cutaneous wound healing
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Wound healing is a well-orchestrated, complex process leading to the repair of injured tissues. Two major proteolytic systems, the matrix metalloproteases and the plasminogen activator system, are involved in this process. The lack of plasminogen (plg) has previously been reported to cause a delay in wound closure in mice, and to be complemented by matrix metalloproteases. However, our previous finding that tympanic membrane perforations in plgdeficient mice do not heal indicated that plg has more important function in wound healing than previously regarded. In later studies, we have found that plg accumulates in the wound early during the healing process and potentiates the inflammatory response and the healing. In the present study, we have used incision and burn wound models in wild-type and plgdeficient mice to further investigate the role of plg in the later phases of the healing process, including its role after re-epithelization. In addition to the earlier observed delay of wound reepithelizationin plg-deficient mice, we have found that the tissue remodeling processes that take place after re-epithelization is also impaired in these mice. By morphological and immunohistochemical analyses, we found that plg-deficient mice had delayed granulationtissue formation, and were unable to clear the provisional matrix. Extensive fibrin deposition and persistent neutrophil infiltration even at day 60 post-wounding indicate that the inflammation was present subcutaneously in plg-deficient mice even at later time points. Importantly, intravenous or subcutaneous supplementation of plg-deficient mice by human plg led to a restored healing rate, and a healing pattern that was comparable to that in wildtype mice. Therefore, in addition to its important function in early stages of cutaneous wound healing, plg is also crucial for later phases, by clearing fibrin deposits and resolving inflammation after full re-epithelization of the wound. Our results suggest that plg may be a potential therapeutic agent for improving the healing of different types of skin wounds.
|
|
| 5. |
- Sulniute, Rima, et al.
(författare)
-
Plasminogen is a critical regulator of cutaneous wound healing
- 2016
-
Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 115:5, s. 1001-1009
-
Tidskriftsartikel (refereegranskat)abstract
- Wound healing is a complicated biological process that consist of partially overlapping inflammatory, proliferation and tissue remodelling phases. A successful wound healing depends on a proper activation and subsequent termination of the inflammatory phase. The failure to terminate the inflammation halts the completion of wound healing and is a known reason for formation of chronic wounds. Previous studies have shown that wound closure is delayed in plasminogen deficient mice, and a role for plasminogen in dissection of extracellular matrix was suggested. However, our finding that plasminogen is transported to the wound by inflammatory cells early during the healing process, where it potentiates inflammation, indicates that plasminogen may also have other roles in the wound healing process. Here we report that plasminogen-deficient mice have extensive fibrin and neutrophil depositions in the wounded area long after re-epithelialisation, indicating inefficient debridement and chronic inflammation. Delayed formation of granulation tissue suggests that fibroblast function is impaired in the absence of plasminogen. Therefore, in addition to its role in the activation of inflammation, plasminogen is also crucial for subsequent steps, including resolution of inflammation and activation of the proliferation phase. Importantly, supplementation of plasminogen-deficient mice with human plasminogen leads to a restored healing process that is comparable to that in wild-type mice. Besides of being an activator of the inflammatory phase during wound healing, plasminogen is also required for the subsequent termination of inflammation. Based on these results, we propose that plasminogen may be an important future therapeutic agent for wound treatment.
|
|
| 6. |
- Wahlberg, Patrik, et al.
(författare)
-
Expression and localization of the serine proteases high-temperature requirement factor A1, serine protease 23, and serine protease 35 in the mouse ovary.
- 2008
-
Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 149:10, s. 5070-7
-
Tidskriftsartikel (refereegranskat)abstract
- Proteolytic degradation of extracellular matrix components has been suggested to play an essential role in the occurrence of ovulation. Recent studies in our laboratory have indicated that the plasminogen activator and matrix metalloproteinase systems, which were previously believed to be crucial for ovulation, are not required in this process. In this study we have used a microarray approach to identify new proteases that are involved in ovulation. We found three serine proteases that were relatively highly expressed during ovulation: high-temperature requirement factor A1 (HtrA1), which was not regulated much during ovulation; serine protease 23 (PRSS23), which was down-regulated by gonadotropins; and serine protease 35 (PRSS35), which was up-regulated by gonadotropins. We have further investigated the expression patterns of these proteases during gonadotropin-induced ovulation in immature mice and in the corpus luteum (CL) of pseudopregnant mice. We found that HtrA1 was highly expressed in granulosa cells throughout follicular development and ovulation, as well as in the forming and regressing CL. PRSS23 was highly expressed in atretic follicles, and it was expressed in the ovarian stroma and theca tissues just before ovulation. PRSS35 was expressed in the theca layers of developing follicles. It was also highly induced in granulosa cells of preovulatory follicles. PRSS35 was also expressed in the forming and regressing CL. These data suggest that HtrA1 and PRSS35 may be involved in ovulation and CL formation and regression, and that PRSS23 may play a role in follicular atresia.
|
|
