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Contains fulltext : 296018.pdf (Publisher’s version ) (Open Access), Mechanisms of infection and pathogenesis have predominantly been studied based on differential gene or protein expression. Less is known about posttranslational modifications, which are essential for protein functional diversity. We applied an innovative glycoproteomics method to study the systemic proteome-wide glycosylation in response to infection. The protein site-specific glycosylation was characterized in plasma derived from well-defined controls and patients. We found 3862 unique features, of which we identified 463 distinct intact glycopeptides, that could be mapped to more than 30 different proteins. Statistical analyses were used to derive a glycopeptide signature that enabled significant differentiation between patients with a bacterial or viral infection. Furthermore, supported by a machine learning algorithm, we demonstrated the ability to identify the causative pathogens based on the distinctive host blood plasma glycopeptide signatures. These results illustrate that glycoproteomics holds enormous potential as an innovative approach to improve the interpretation of relevant biological changes in response to infection.

For small, arboreal marmoset monkeys, antipredator vigilance is essential to ensure survival. However, since antipredator vigilance is incompatible with some other behaviours, such as feeding in a head-down position, it has to be regulated efficiently within individuals and perhaps even at the group level. To investigate what drives individual differences in vigilance and feeding behaviour in common marmosets, Callithrix jacchus, and whether they adjust these behaviours to each other, we collected behavioural data on 14 marmosets in contexts where feeding and vigilance were mutually exclusive. The presence of infants resulted in higher overall vigilance and less feeding. Moreover, individuals increased their vigilance when the pair mate was feeding and thus could not be vigilant itself. They thus adjusted their own vigilance to the risk level of their pair mate, which resulted in a turn taking-like pattern of feeding and being vigilant in the pair. This flexibility of vigilance is consistent with marmosets' sensitivity to other's needs in another context, food sharing, when sharing is increased when food is more difficult to obtain. Together, these results suggest considerable awareness of the current state of group members in common marmosets.

Ruimtelijke planning en milieubeleid groeien naar elkaar toe onder impuls van het omgevingsdenken.1 Voor de OVAM, met een unieke positie in het sturen van bodemsaneringsbeleid en het aanjagen van de transitie naar een circulaire economie, is dit een evolutie die volop steun verdient. De zoektocht naar meer integratie, afstemming en samenwerking in het omgevingsbeleid, start niet vanaf nul.

Radboud University, 07 december 2021, Promotores : Groot, R. de, Gool, A.J. van Co-promotores : Jonge, M.I. de, Gloerich, J., Contains fulltext : 240234.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 236802.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 244088.pdf (Publisher’s version ) (Open Access), Age-related macular degeneration (AMD) is a major cause of vision loss among the elderly in the Western world. The complement system has been identified as one of the main AMD disease pathways. We performed a comprehensive expression analysis of 32 complement proteins in plasma samples of 255 AMD patients and 221 control individuals using mass spectrometry-based semi-quantitative multiplex profiling. We detected significant associations of complement protein levels with age, sex and body-mass index (BMI), and potential associations of C-reactive protein, factor H related-2 (FHR-2) and collectin-11 with AMD. In addition, we confirmed previously described associations and identified new associations of AMD variants with complement levels. New associations include increased C4 levels for rs181705462 at the C2/CFB locus, decreased vitronectin (VTN) levels for rs11080055 at the TMEM97/VTN locus and decreased factor I levels for rs10033900 at the CFI locus. Finally, we detected significant associations between AMD-associated metabolites and complement proteins in plasma. The most significant complement-metabolite associations included increased high density lipoprotein (HDL) subparticle levels with decreased C3, factor H (FH) and VTN levels. The results of our study indicate that demographic factors, genetic variants and circulating metabolites are associated with complement protein components. We suggest that these factors should be considered to design personalized treatment approaches and to increase the success of clinical trials targeting the complement system.

Contains fulltext : 229301.pdf (publisher's version ) (Open Access), OBJECTIVES: Complement deficiencies are difficult to diagnose because of the variability of symptoms and the complexity of the diagnostic process. Here, we applied a novel 'complementomics' approach to study the impact of various complement deficiencies on circulating complement levels. METHODS: Using a quantitative multiplex mass spectrometry assay, we analysed 44 peptides to profile 34 complement proteins simultaneously in 40 healthy controls and 83 individuals with a diagnosed deficiency or a potential pathogenic variant in 14 different complement proteins. RESULTS: Apart from confirming near or total absence of the respective protein in plasma of complement-deficient patients, this mass spectrometry-based profiling method led to the identification of additional deficiencies. In many cases, partial depletion of the pathway up- and/or downstream of the absent protein was measured. This was especially found in patients deficient for complement inhibitors, such as angioedema patients with a C1-inhibitor deficiency. The added value of complementomics was shown in three patients with poorly defined complement deficiencies. CONCLUSION: Our study shows the potential clinical utility of profiling circulating complement proteins as a comprehensive read-out of various complement deficiencies. Particularly, our approach provides insight into the intricate interplay between complement proteins due to functional coupling, which contributes to the better understanding of the various disease phenotypes and improvement of care for patients with complement-mediated diseases.