Thesis focused on uncovering the underlying mechanisms of the lysosomal storage disorders Gaucher's disease using chemical tools, biochemical assays and lipidomics.

This thesis is devoted to an in-depth examination of the various effects of disorder in the cuprate high-temperature superconductors.

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Lysosomal storage disorders (LSDs) are a group of orphan diseases characterized by lysosomal dysfunction or impaired lysosomal catabolism and affect collectively about 1 in 5000 live births.

Lysosomal glycosidases are acid hydrolases that fragment glycoconjugates in lysosomes.

Neurodegenerative diseases pose a large medical and societal challenge. The etiology of these diseases is still poorly understood, which makes drug discovery for these diseases difficult.

The research described in this thesis combines the latest insights in lysosomal function with lysosome centred cell signalling.

Advanced mass spectrometry of glycosphingolipids takes the central stage in this thesis. Investigations focus on characterization of glycosphingolipid metabolism in health and disease with emphasis to the detection and accurate quantitation of known and so far unknown glycosphingolipids and closely…

Emoties en de psychosociale ontwikkeling van kinderen met en zonder Taal Ontwikkelingsstoornis

Promotie

Promotores: H.S. Overkleeft, G.A. van der Marel, Co-promotor: B.I. Florea

The lysosomal β-glucosidase named glucocerebrosidase (GCase) is a retaining β-glucosidase that hydrolyzes the glycosphingolipid glucosylceramide (GlcCer) to ceramide and glucose at acid pH.

N-acylethanolamines (NAEs), including N-arachidonoylethanolamine (anandamide, AEA), N-palmitoylethanolamine (PEA) and N-oleoylethanolamine (OEA), are signaling lipids that play an important role in different physiological process.

The studies described in this thesis deal with glycosidases, in particular alpha-galactosidases.

Glycosidases are essential in fundamental biological processes and are responsible for the degradation of most (oligo)saccharides, glycolipids and glycoproteins.

Promotor: Prof.dr.ir. J.W.M. Hilgenkamp, Prof.dr. J. van den Brink

The main aim of my Ph.D. thesis is to further explore the value of using early developing zebrafish larvae (up to 5 dpf) as a model to study anxiety-like behaviour and their pharmacological modulation with drugs.

Voor veel scheikundigen aan de universiteit is het de ultieme droom: een middel ontwikkelen dat écht bij patiënten terechtkomt. Maar de weg daarnaartoe is lang en onzeker. Nu mag het Leidse middel nizubaglustat door naar de derde fase van klinisch onderzoek. Dat is mogelijk dankzij een investering van…

Gaucher disease is a rare metabolic disorder, in which a mutation of the enzyme glucocerebrosidase (GBA1) causes buildup of its substrate glucosylceramide and the deacylated counterpart glucosylsphingosine in lysosomes.

In een recente studie tonen dr. Moji Aghajani en collega’s aan dat jongeren met een ernstige vorm van Conduct Disorder (CD) -met beperkte prosociale emoties- opvallend veel hersencapaciteit nodig hebben om emotionele gezichten te kunnen lezen. Deze effecten werden gevonden in vergelijking met CD-jongeren…

Advanced UHF MRI techniques provide powerful tools for studying the zebrafish brain, an emerging model in neurological research. In this work, various MRI and localized MRS methods are optimized and employed for UHF strength for studying the zebrafish brain.

Promotor: Prof.dr. C.W.J. Beenakker

This thesis consists of three papers that are centered around the common theme of Hausdorff uo-Lebesgue topologies and convergence structures on vector lattices and on vector lattices and vector lattice algebras of order bounded operators.

The research described in this thesis has, using the zebrafish as a model system, shed new light on the intricate relationship between TB and DM2, in particular on the role of leptin, SHP-1 and glucocorticoids.

The ideas underlying this thesis are that lipidomics may improve the diagnosis of liver metabolic diseases, and can provide further insights into the underlying pathophysiology of these diseases.

Optimalisatie, werkingsmechanismen en voorspellers van het resultaat van lichttherapie bij depressie: Een multicenter gerandomiseerde trial

This thesis describes biochemical investigations of glucocerebrosidase (GBA), the lysosomal β- glucosidase that is deficient in Gaucher disease (GD).

The research described in this thesis centered on retaining exo-β-glucosidases implicated in health and disease, in particular the human inherited lysosomal storage disorder, Gaucher disease (GD).

The long-held desire - to link structure directly to function and to explain molecular mechanisms based on basic chemical or physical principles - is finally coming closer, satisfying not only our scientific curiosity but also offering new solutions to the many challenges in the field of health, energy…

Studying the impact of urbanisation on the respiratory health of past Dutch populations (1200-1850 CE).

Promotor: E.F. Smets Co-promotor: J. Geml

This Thesis describes the design, synthesis and evaluation as glycoprocessing enzyme inhibitors of focused libraries of iminosugars.

Vast, often populated, areas in dryland ecosystems face the dangers of desertification.

In this thesis, we have used numerical approaches to study the effects of translational symmetry breaking on strange metallic systems as realised by the holographic duality⁠.

Lezing

Samen met wetenschappers van over de hele wereld streeft de ENIGMA-Anxiety Werkgroep ernaar om meer inzicht te krijgen in de neurobiologische karakteristieken van angststoornissen.

Promotor: K. Kuijken, Co-Promotor: H. Hoekstra

In this thesis, we study systems of electrons in which strong correlations give rise to emergent exotic physics.

The redox-conversion reaction of metal-disulfide and metal-thiolate complexes are important, as they may shed light on electron-transfer reactions that often occur in Nature.

In this thesis, bioorthogonal chemistry is combined with correlative light-electron microscopy to selectively label and study pathogenic intracellular bacteria within the host immune cell.

Control of infectious diseases poses continuous challenges for human health.

The effective treatment of tuberculosis (TB) remains a major challenge to global health.

Glycoside hydrolases (glycosidases/GHs) are widely abundant enzymes in all kingdoms of life and are important biocatalysts that catalyze the hydrolysis of glycosidic linkages in oligo/polysaccharides, glycoproteins and glycolipids with tremendous efficiency

Een lijst met wetenschappelijke publicaties samengesteld door het team van het TRIXY Expertisecentrum.

The dissertation offers new tools and insights to computation and modelling of topological phases, with an emphasis on the aperiodic setting.

A neurocognitive investigation of the development of social performance monitoring in youth growing up in stressful versus non-stressful environments

Promotor: Prof.dr. J. den Hertog