Mads Ronald Dahl

MASP-3 and Its Association with Distinct Complexes of the Mannan-Binding Lectin Complement Activation Pathway

The mannan-binding lectin (MBL) pathway of complement activation is part of the innate immune defense. The binding of MBL to microbial carbohydrates activates the MBL-associated serine proteases (MASPs), which recruit the complement factors, C4 and C2, to generate the C3 convertase or directly activate C3. We present a phylogenetically highly conserved member of the MBL complex, MASP-3, which is generated through alternative splicing of the MASP-1/3 gene. The designation of MASP-3 as a protease is based on homology to known MASPs. Different MBL oligomers were found to have distinct MASP composition and biological activities. MASP-1, MAp19, and direct C3-cleaving activity are associated with smaller oligomers whereas MASP-3 is found together with MASP-2 on larger oligomers. MASP-3 downregulate the C4 and C2 cleaving activity of MASP-2.

Murine serine proteases MASP-1 and MASP-3, components of the lectin pathway activation complex of complement, are encoded by a single structural gene

Activation of the lectin pathway of complement is initiated by the binding to microbial carbohydrate structures of a multimolecular fluid-phase complex composed of a carbohydrate recognition subcomponent that associates with three specific serine proteases and an enzymatically inert protein of 19 kDa. The first carbohydrate recognition subcomponent of the lectin pathway identified was mannan-binding lectin (MBL), hence the serine proteases were named MBL-associated serine proteases (MASPs) and numbered according to the sequence of their discovery. Here we describe the primary structures of the two distinct serine proteases MASP-1 and MASP-3 in the rat (and of MASP-3 in the mouse), show their association with plasma MBL complexes, and demonstrate that in rat and mouse, as in man, MASP-1 and MASP-3 are encoded by a single structural gene. For both species, we present the genomic region and regulatory elements responsible for the processing of either MASP-1 or MASP-3 mRNA by alternative splicing/alternative polyadenylation. Furthermore, we demonstrate the evolutionary conservation of MASP-3 mRNA in cDNA transcripts from guinea pig, rabbit, pufferfish, and cow.

Survey of attitudes towards curriculum reforms among medical teachers in different socio-economic and cultural environments

Background: Curriculum reforms in medical schools require cultural and conceptual changes from the faculty. Aims and Methods: We assessed attitudes towards curriculum reforms in different academic, economic, and social environments among 776 teachers from 2 Western European medical schools (Belgium and Denmark) and 7 medical schools in 3 countries in post-communist transition (Croatia, Slovenia, Bosnia and Herzegovina). The survey included a 5-point Likert-type scale on attitudes towards reforms in general and towards reforms of medical curriculum (10 items each). Results: Teaching staff from medical schools in Bosnia and Herzegovina had a more positive attitude towards reforms of medical curriculum (mean score 36.8 out of maximum 50 [95% CI 36.1 to 37.3]) than those from medical schools in Croatia or Slovenia (30.7 [29.8 to 31.6]) or Western Europe (27.7 [27.1 to 28.3]) (P < 0.001, ANOVA). Significant predictors of positive attitudes towards medical curriculum reform in post-communist transition countries, but not in Western European schools, was younger age, as well as female gender in Bosnia and Herzegovina. Conclusions: Factors influencing faculty attitudes may not be easy to identify and may be specific for different settings. Their identification and management is necessary for producing sustainable curriculum reform.

What you see is not what you get in the PDF document format

The sharing and storage of scientific knowledge, information and data are today mainly in digitized form, which will become the predominant means of communicating scientific work in the future. One of the best-established formats is the open standard of PDF (Portable Document Format), which is renowned for its flexibility and stability. In this article, we expose a major flaw in the format with respect to the security of confidential information, such that even organizations responsible for safeguarding and setting the standards for data management were unintentionally revealing confidential patient data. By collecting and analysing a random sample of files from a health informatics organization, we demonstrate the extent of the problem and determine its cause by code analysis of an example. In conclusion, we suggest the development of a knowledge-sharing format that does not demand expert skills for safe usage: WYSIWYS (What You See Is What You Store).

An Assay for Mannan‐Binding Lectin‐Associated Serine Protease 3, MASP‐3

The mannan‐binding lectin (MBL) pathway is part of the innate immune system providing a first line of defence against infections. MBL and ficolins circulate in complexes with MBL‐associated serine proteases (MASP‐1, ‐2 and ‐3). After recognition of a microorganism by MBL, activation of the complement system occurs. MASP‐1 and MASP‐3 share five domains (making up the so‐called A‐chain), whereas they have unique protease domains (B‐chains). Before the identification of MASP‐3, an assay for MASP was presented, based on antibodies against the A‐chain of MASP‐1. With the new knowledge of the three MASPs, and the sharing of domains by MASP‐1 and MASP‐3, assays specific for the protease domains have to be constructed, if one wishes to measure the proteins individually. We present an assay for quantifying total MASP‐3 in plasma and serum samples. The assay is a sandwich‐type assay using as catching antibody a monoclonal antibody against the common A‐chain of MASP‐1/3 and a developing secondary antibody against the C‐terminal part of the protease domain of MASP‐3. We have used this assay for estimating the normal concentration of the protein as well as the concentration in patients and also for characterizing by gel permeation chromatography the MASP‐3 protein in serum.