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Necrotizing Enterocolitis: The Role of Intestinal Alkaline Phosphatase in the Developing Gut
No full textNecrotizing enterocolitis (NEC) is a severe gastrointestinal disease predominantly affecting extremely premature infants and remains a major cause of neonatal morbidity and mortality. Increasing evidence suggests that NEC represents a spectrum of conditions driven by immaturity of intestinal immunity rather than a single disease entity. This thesis focuses on NEC associated with extreme prematurity and investigates the role of intestinal alkaline phosphatase (IAP) in its pathophysiology.IAP is an apical enterocyte enzyme involved in detoxifying lipopolysaccharide (LPS) and modulating inflammatory signaling through Toll-like receptor 4 (TLR4). Using intestinal resection specimens, we demonstrated significantly reduced ileal IAP expression and enzymatic activity in NEC patients compared with controls. We also observed apical co-localization of IAP and TLR4, supporting a functional interaction relevant to intestinal inflammation. Developmental analyses of fetal ileum revealed that IAP expression emerges between 21 and 30 weeks of gestation, whereas TLR4 is expressed from early gestation onward, highlighting a developmental imbalance that may predispose the preterm gut to excessive inflammatory responses.In addition, clinical analyses identified blood group AB as a significant risk factor for severe NEC and NEC related mortality, independent of fetal–maternal blood group incompatibility. These findings suggest potential links between ABO blood group, IAP related pathways, and NEC severity. Together, this work identifies IAP as a key modulator of intestinal immune homeostasis in the immature gut and supports its potential as a therapeutic target for preventing or mitigating NEC in vulnerable preterm infants
De zorgwekkende actualiteit van regimewisseling
No full textDe arrestatie van de Venezolaanse president Maduro laat zien dat Amerikaanse interventie in de binnenlandse politiek van andere landen allerminst een historisch verschijnsel is uit de Koude Oorlog. Ook toen speelden de Verenigde Staten wereldwijd een actieve rol bij het omverwerpen van communistische regimes en het onderdrukken van communistische bewegingen. Nu de Nederlandse vertaling van Vincent Bevins’ De Jakartamethode is verschenen, vraagt historicus Clemens Six zich af of dit boek ook nieuwe, actuele inzichten biedt in hedendaagse regimewisselingen.De arrestatie van de Venezolaanse president Maduro laat zien dat Amerikaanse interventie in de binnenlandse politiek van andere landen allerminst een historisch verschijnsel is uit de Koude Oorlog. Ook toen speelden de Verenigde Staten wereldwijd een actieve rol bij het omverwerpen van communistische regimes en het onderdrukken van communistische bewegingen. Nu de Nederlandse vertaling van Vincent Bevins’ De Jakartamethode is verschenen, vraagt historicus Clemens Six zich af of dit boek ook nieuwe, actuele inzichten biedt in hedendaagse regimewisselingen
Ionization potential of radium monofluoride
No full textThe ionization potential (IP) of radium monofluoride (RaF) was measured to be 4.969(2)[10] eV, revealinga relativistic enhancement in the series of alkaline earth monofluorides. The results are in agreement with arelativistic coupled-cluster prediction of 4.981(7) eV, incorporating up to quantum electrodynamics corrections.Using the same computational methodology, an improved calculation for the dissociation energy (D0) of5.54(5) eV is presented. This confirms that RaF joins the group of diatomic molecules for which D0 > IP,paving the way for precision control and interrogation of its Rydberg states
Alterations in lipid, redox, and energy metabolism in recent onset psychosis:a metabolomics study in non-smoking individuals and matched controls
No full textPsychotic disorders are associated with systemic metabolic alterations, but these associations may be confounded by smoking. We investigated plasma metabolites in 47 non-smoking recent onset psychosis patients and 36 matched (on age, sex and ethnicity) healthy controls using untargeted LC MS metabolomics. We applied univariate, multivariate and pathway analyses, with subgroup exploration in patients that were diagnosed with schizophrenia spectrum disorder (SSD) specifically. We identified 28 significantly altered metabolites predominantly reflecting lipid metabolism (elevated saturated free fatty acids, glycerol 3 phosphate, conjugated bile acid), redox imbalances (decreased L cysteine, L cystine and taurine) and energy metabolism (reduced pyruvate). These alterations remained significant after adjusting for sex, antipsychotic treatment and metabolic syndrome parameters. Enrichment analyses highlighted taurine/hypotaurine metabolism, alanine/aspartate/glutamate pathways and fatty acid biosynthesis in psychosis. Within the SSD subgroup (n = 28), metabolic perturbations were more pronounced, showing stronger depletion of reducing equivalents and elevated free fatty acids. These findings indicate a specific systemic metabolic signature in psychosis independent of smoking, sex, antipsychotic medication or metabolic syndrome. The pattern suggests mitochondrial dysfunction and increased oxidative stress, accompanied by compensatory lipid mobilization. These findings identify redox and energy metabolism as promising targets for future pharmacological or metabolic interventions in SSD.</p
Genetic Insights in Hindbrain Abnormalities Through Network Analysis Expose Key Biological Pathways in Hindbrain Development
No full textThe number of known developmental disorders affecting the hindbrain is rapidly increasing due to advances in neuroimaging and genetic technologies. Nevertheless, it remains largely unknown why the development of the hindbrain is affected in many genetic disorders. We aim to unveil new insights into the biological pathways essential for hindbrain development by investigation of the pathogenetics of hindbrain abnormalities. In this work, an updated gene list of abnormalities of the hindbrain was generated, and genes were subsequently grouped according to most prevalent association in (1) predominantly cerebellar, (2) cerebellar and brainstem and (3) brainstem malformations. Brain-specific gene co-expression networks were generated to identify functional relationships and novel genes that were not yet linked to hindbrain malformations. The results showed that shared biological pathways underlie distinct hindbrain processes, even when cells originate from different primordia. Key players in hindbrain development include genes encoding transcription factors and extracellular signaling molecules. Notably, brainstem abnormalities are biologically distinct, with a smaller role for ciliogenesis. Through co-expression analysis, we identified candidate genes for hindbrain malformations including TRRAP and NCAM1. The identification of essential biological pathways in this study uncovers additional important challenges in genetic hindbrain malformations, such as how defects in apparently ubiquitous processes result in brain-specific phenotypes, and how timing and repair mechanisms influence the pathogenesis of affected pathways.</p
A 28-year record of the isotopic niche of baleen whales in the Gulf of St. Lawrence, Canada:A perspective on ecosystem changes and potential for food competition.
No full textFin whales (Balaenoptera physalus), humpback whales (Megaptera novaeangliae)and minke whales (Balaenoptera acutorostrata) seasonally coexist in sympatry inthe Gulf of St. Lawrence (Canada) where they feed to replenish their energyreserves. Over the past decades, these three species have experienced significantshifts in resource availability as the St. Lawrence ecosystem encountered majortrophodynamic changes due to climatic and anthropogenic perturbations. Thisstudy aimed to understand how the realized trophic niche of these rorqualspecies has changed over time. To achieve this objective, stable nitrogen andcarbon isotope ratios from 1110 whale skin biopsies sampled between 1992 and2019 were used to define the isotopic niche of each species, quantify their dietusing Bayesian isotopic mixing models, and assess the degree of individual dietspecialization. Resource partitioning among these three sympatric speciesincreased during the 2011–2019 period, as highlighted by the limited overlapobserved among their isotopic niches. A recent dietary shift toward an increasedreliance on pelagic fish (capelin, herring and/or mackerel) in fin whale and minkewhale and a reduced contribution of krill suggests a possible reduction in krillabundance in the Gulf of St. Lawrence in recent years. These findings provide aunique insight into the ability of three generalist species to coexist throughpartitioning food resources, and adapt to ecosystem changes. Given the climaticcontext, knowledge of preferred prey is crucial for the conservation ofthese species
Broadening STEM participation:An intersectional approach to promoting minoritised students’ inclusion
No full textThis dissertation examines the systemic marginalization of LGBTQIA+ individuals (hereafter referred to as queer) in Science, Technology, Engineering, and Mathematics (STEM) education and professional environments, and argues for the urgent need to reimagine STEM through inclusive and justice-centered frameworks. Rather than treating queer lives as exceptions to be accommodated, this research positions them as central to transforming what STEM education is, does, and can become.Grounded in queer theory and intersectionality, the dissertation interrogates how power operates through normative assumptions embedded in science and education. Queer theory is used to challenge binary constructions of gender and sexuality and to disrupt dominant norms, while intersectionality highlights how interlocking systems of oppression—including cisheteronormativity, racism, ableism, classism, and patriarchy—shape lived experiences and access to STEM. Together, these frameworks support a research agenda that centers lived experience, resists assimilation, and seeks systemic transformation.The dissertation consists of five articles. The first presents a systematic review of 24 empirical studies on queer individuals in STEM learning and working environments, revealing persistent patterns of exclusion, harassment, and professional marginalization. The second article is a multiple case study of three queer individuals, using life-history interviews to examine how dominant cultural models in science shape science identity trajectories. The third article foregrounds queer perspectives on transforming STEM education through changes in culture, curriculum, pedagogy, and relationships. The fourth article develops a teacher training course focused on diversity, inclusion, and social justice in STEM, translating theory into practice. The fifth article analyzes instructional materials created by participating teachers, identifying both promising practices and ongoing challenges.Overall, this dissertation contributes theoretical, empirical, and practical tools for advancing more inclusive and liberatory STEM education
Towards understanding cyclic di-AMP metabolism
No full textBacteria rely on small signaling molecules to rapidly adapt to changes in their environment. One such molecule, cyclic di-AMP, has emerged over the past decade as an essential regulator of bacterial physiology. This thesis investigates how cyclic di-AMP is synthesized, broken down, and used by bacteria to maintain their viability in a dynamic external environment.Chapter 1 places cyclic di-AMP in a broader physiological context, showing that its primary role is to control bacterial cell volume. By regulating the movement of ions and small molecules across the cell membrane, cyclic di-AMP allows cells to maintain internal pressure and adapt to osmotic stress. The chapter then explores how other essential cell processes are connected to cyclic di-AMP signaling, for example, cell wall synthesis, DNA replication and the stringent response, and how they are connected to cell volume control.Chapter 2 focuses on the enzyme responsible for cyclic di-AMP synthesis, CdaA. Using a combination of biochemical and structural methods, chapter 2 demonstrates that CdaA may only synthesize cyclic di-AMP efficiently when membrane-embedded, where it forms an active complex.Chapter 3 examines how cyclic di-AMP is broken down. Chapter 3 focuses on NrnA and GdpP, enzymes that are required for breakdown of cyclic di-AMP to pApA (GdpP) and finally from pApA to AMP (NrnA). NrnA is an enzyme essential which maintains bacterial viability, but which does not directly degrade cyclic di-AMP. Instead, NrnA clears the potentially toxic accumulation of dinucleotide breakdown products, like pApA.Together, this thesis presents a clear and concise investigation into cyclic di-AMP signalling, followed by investigation of key cyclic di-AMP metabolic enzymes, and finishes by exploring the implications of cyclic di-AMP research in microbial physiology and future development of cyclic di-AMP-targeted antibacterial therapies
Advancing Tools to Assess Visual Crowding in Healthy Vision and Glaucoma
No full textSeeing the world clearly is not only about sharp eyesight. Much of what we do every day, reading street signs, finding a friend in a crowd, or safely navigating busy environments, depends on how well we can recognize objects in our peripheral vision. In many people, including those with eye diseases such as glaucoma, this ability is limited by a phenomenon called visual crowding: when objects are close together, they become difficult to identify, even if they are not blurred. Although crowding has major consequences for daily life, it is rarely measured in clinical practice, largely because existing tests are slow or cumbersome.This thesis set out to improve how we measure crowding and to understand when and why it changes. I developed several new, rapid and more engaging methods that use eye tracking and continuous measurements to assess peripheral vision. These tools make it possible to measure crowding rapidly instead of lengthy test sessions. I then investigated whether crowding is affected by factors such as light level, showing that crowding remains remarkably stable across bright and dim environments. Finally, I explored how crowding behaves in glaucoma, a disease that damages the optic nerve and leads to blindness if untreated. My findings suggest that the increased crowding seen in early glaucoma may provide insights into functional difficulties that are not captured by standard clinical tests.Overall, this work advances our ability to measure and understand peripheral vision, offering new possibilities for earlier and more meaningful assessment of visual disorders like glaucoma
Pre-adolescent learners' foreign language classroom anxiety profiles and correlates:Insights from Chinese primary school students of English
No full textThis paper reports on a study investigating the level and correlates of foreign language classroom anxiety among pre-adolescent students. The participants were 385 L1 Chinese primary school students of L2 English, aged between 8 and 13 (with a mean age of 10.73), who completed a validated English Classroom Anxiety Scale and a questionnaire tapping: (1) three learner-centered predictor variables (i.e., gender; attitudes towards English, and perceived relative standing among peers in English proficiency; The participants’ age was provided by their parents or caregivers) and (2) six teacher-centered predictors (i.e., attitudes towards the English teacher; teacher strictness, friendliness, joking, and predictability; and the frequency of the teacher’s English usage in class). Data analysis showed that the participants generally experienced a moderately low level of English classroom anxiety. English classroom anxiety showed no significant difference among Years 3 to 5 participants but significantly decreased in Year 6. Girls and boys did not differ significantly in their English classroom anxiety levels. Attitudes towards English, attitudes towards the English teacher, perceived relative standing among peers in English proficiency, and age significantly negatively predicted English classroom anxiety, in descending order of magnitude. Teacher friendliness and the teacher’s frequency of English usage in class significantly and negatively predicted English classroom anxiety but only marginally so. Three variables under consideration, teacher joking, strictness, and predictability, were not significant predictors of English classroom anxiety. The results and their (pedagogical) implications are discussed and the limitations of this study are put forward