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Klinische vooruitzichten van immuuncel-subtypes bij neuro-inflammatoire aandoeningen via single-cell transcriptomics
No full textMultiple sclerosis (MS) is a common neuroinflammatory disorder. MS typically affects young adults and can lead to important physical and cognitive disability at a crucial stage in their life. There are approximately 13,500 individuals suffering from the disease in Belgium, and 2.5 million worldwide. Characteristics of the disease are inflammation, demyelination and axonal loss in brain and spinal cord. In collaboration with colleagues worldwide of the International Multiple Sclerosis Genetics Consortium we have identified more than 200 genetic risk factors for MS in the last years. Our research group has also been pioneering in moving beyond susceptibility to understand the important heterogeneity, that is patient-to-patient variation in disease course and response to treatment. Despite these successes, both for both susceptibility and heterogeneity only a fraction of the entire heritability has now been identified. The current PhD project focuses on the remaining interindividual variation in susceptibility and heterogeneity in MS and postulates new hypotheses on novel sources of genetic variation as the explanation. With a background as MD and Neurology resident, the PhD candidate will be excellently placed to combine clinical data of MS patients with biological data obtained from samples of the same patients. For the generation of biological data, state-of-the-art genetic methods such as next-generation sequencing and single-cell sequencing are applied, followed by data integration, bio-informatics and statistical analysis.status: Publishe
Challenging Boundaries: Exploring Pricing Strategies, and Unpaid Labour Time to Explain Earning Disparities in Online Labour Markets
No full textThis paper challenges the prevailing perception of the boundless nature of Online Labour Markets (OLMs), where platforms connect service providers, such as online freelancers or workers, with clients. The focus is specifically on the pricing strategies employed by online freelancers on Upwork, a prominent international freelance platform. This article contributes empirically and theoretically to debates on the purported boundlessness of OLMs. It illustrates how online freelancers, when confronted with the rules and practices of platform algorithms, develop distinct strategies to navigate the challenges and access work across regional boundaries. Importantly, our findings reveal that despite adopting similar pricing strategies there are earnings disparities among freelancers across regional boundaries. Consequently, unpaid labour time incurred by workers in developing countries while providing services through the platform becomes a discernible cost borne by freelancers in their pursuit of accessing more lucrative opportunities.sponsorship: This work was supported by ERC-AdG funded "ResPecTMe" project: [Grant agreement no 833577]. (ERC-AdG|833577, European Research Council (ERC)|833577)status: Published onlin
Emerging Concepts and Success Stories in Type 1 Diabetes Research: A Road Map for a Bright Future
No full textType 1 diabetes treatment stands at a crucial and exciting crossroad since the 2022 U.S. Food and Drug Administration approval of teplizumab to delay disease development. In this article, we discuss four major conceptual and practical issues that emerged as key to further advancement in type 1 diabetes research and therapies. First, collaborative networks leveraging the synergy between the type 1 diabetes research and care community members are key to fostering innovation, know-how, and translation into the clinical arena worldwide. Second, recent clinical trials in presymptomatic stage 2 and recent-onset stage 3 disease have shown the promise, and potential pitfalls, of using immunomodulatory and/or β-cell protective agents to achieve sustained remission or prevention. Third, the increasingly appreciated heterogeneity of clinical, immunological, and metabolic phenotypes and disease trajectories is of critical importance to advance the decision-making process for tailored type 1 diabetes care and therapy. Fourth, the clinical benefits of early diagnosis of β-cell autoimmunity warrant consideration of general population screening for islet autoantibodies, which requires further efforts to address the technical, organizational, and ethical challenges inherent to a sustainable program. Efforts are underway to integrate these four concepts into the future directions of type 1 diabetes research and therapy.sponsorship: Acknowledgments. The authors thank Dr. Emily Anderson-Baucum (Indiana University School of Medicine) and Amanda Posgai (University of Florida) for assistance in editing the text of the manuscript. (Veteran Affairs)status: Publishe
De Pauselijke Bijbelcommissie: haar geschiedenis, werkwijze, en belangrijkste documenten
No full textstatus: Publishe
Baldwin's European Digital Circulation: More Tweets of a Native Son
No full textFor the past decade, James Baldwin’s newly accrued world literary value has been routinely linked to his presence in the digital sphere. This link has reinforced the default assumption of the Anglophone nature of Baldwin’s circulation, without much attention to linguistic and cultural differences. This essay proposes to trace a more diversified account of Baldwin’s online footprint in the wake of Raoul Peck’s seminal I Am Not Your Negro and the transatlantic reverberations of the Black Lives Matter movement through three crucial vectors: X (formerly Twitter), Google Search, and the pageviews of the biographical Baldwin entries on Wikipedia in French, German, and Dutch. Building on Melanie Walsh’s work on Baldwin’s circulation on Anglophone Twitter during the early years of the Black Lives Matter movement, we aim to excavate the intersections and tensions between different dynamics of online circulation in the non-Anglophone European sphere.status: Publishe
TANDHEELKUNDIGE WEEFSELBIOLOGIE TIJDENS ORTHODONTISCHE TANDVERPLAATSING
No full textOrthodontic tooth movement (OTM) is based on the principle of applying forces to a tooth for a certain period of time, which evokes a pronounced biological reaction in the dental pulp (DP), periodontal ligament (PDL), alveolar bone and gingiva. The biologic responses of PDL have been systematically investigated at a molecular, cellular, and tissue-level. However, most studies have been performed in animals and the role of the different molecules has been separately tested either in vivo or in vitro. Studies exploring the effects of orthodontic force (OF) on the DP have showed that increased OF involves pulp cell damage and inflammation. Knowledge regarding the details of the conversion from mechanical forces to biochemical signals on human PDL and DP tissue is still deeply lacking, which would have a significant impact on daily dental and orthodontic practice. Clinically, it is known that OTM results from a complex array of interacting biologic factors. Variables such as age and gender strongly influence the rate of OTM. Ageing affects PDL and DP homeostasis: the PDL becomes more fibrotic during maturation and the root apex narrows by deposition of secondary dentin and cementum, which compromises the blood supplies and nerve tissue passing through the apical foramen. Moreover, PDL biology might be altered in patients of different sex, since hormones are considered to be key mediators in the complex interplay guiding OTM. Therefore, understanding age- and sex-dependent responses of dental tissue to OF can optimize our selection of force systems to provide more efficient and safer treatment for all patients.status: Publishe
Representatie leren in beeldgebaseerde genetica: Nieuwe methoden voor de studie van craniofaciale genetica
No full textThe rapid advancements in modern technology have revolutionized biomedical research, enabling the collection of multimodal data, including genetic, epigenetic, imaging, clinical, and lifestyle information. This has led to the emergence of imaging genetics, an interdisciplinary field that combines imaging technologies like 3D surface scanning with genetic data to identify links between genetic variants and imaging-derived phenotypes. By leveraging AI, machine learning, and statistical genetics, researchers can analyze these complex multimodal datasets to advance diagnostics of genetic diseases, evolutionary biology, and forensic investigations. However, the high-dimensional and correlated nature of imaging and genetic data poses significant computational challenges.
This thesis focuses on developing biologically meaningful, lower-dimensional representations of both phenotypic and genotypic data to enhance the efficiency of genotype-phenotype association analyses. The work is structured into three main components: (i) genotypic data analysis, (ii) phenotypic data analysis, and (iii) integrated genotype-phenotype methods.
First, we explored traditional principal component analysis (PCA) and neural network-based approaches, such as autoencoders (AE), for genotypic data analysis. A novel hybrid model, the singular autoencoder generalized by Identity-by-State (SAE-IBS), was developed to combine the strengths of both methods. This model effectively handled missing or erroneous genotypes and accounted for relatedness, demonstrating improved performance in genetic clustering and ancestry inference.
Second, in phenotypic data analysis, we conducted the first comprehensive comparison of methods for extracting 3D image-derived traits in genome-wide association studies (GWAS). Traditional anthropometric traits, such as inter-landmark distances, exhibited high SNP heritability but limited GWAS discovery due to sparse landmarks. AE traits also showed high heritability but identified fewer GWAS hits compared to PCA. In contrast, resemblance scores to random facial gestalts identified the highest number of genomic loci, offering a promising and easy-to-implement method.
While standard approaches like PCA prioritized capturing geometric variation in shape, they often failed to highlight the most genetically relevant features. To address this, in the third component, we introduced a biologically informed, optimization-based phenotyping strategy to enhance genetic discovery. In GWAS, the framework optimized for high heritability, while in rare variant association studies (RVAS), it aimed to optimize the skewness of phenotype distributions (an indicator of major gene effects). The proposed approach proved more efficient in GWAS and RVAS discovery compared to traditional methods.
Overall, our findings demonstrate that integrating biological information enables more intelligent feature extraction, with optimized approaches outperforming selection-based and unsupervised dimension reduction methods in population structure inference and phenotype extraction for both common and rare genetic variant discovery. This thesis provided a novel perspective for investigating the genetic basis of craniofacial morphology, offering an efficient alternative to traditional methods.status: Publishe
Triangulating the composite system for the protection of European fundamental rights: in the shadow of Article 6 TEU.
No full textsponsorship: Institute for European Law of KU Leuven|RESHUFFLE - 851621 funded by ERCstatus: Accepte
Het mogelijk maken van voedingsverschuivingen in de transformatie van voedselsystemen: van een efficiëntie- naar een toereikendheidsparadigma
No full textIn the triple challenge of the climate, biodiversity and justice crisis, food systems play a significant role. Indeed, they are major drivers of climate change and biodiversity loss as well as other environmental pressures. In addition, strong social inequalities in food systems leads to food insecurity and its associated burdens. To address these challenges, linked to unsustainable consumption patterns, and remain within Earth's carrying capacity, a radical transformation of our food system is necessary. In this transformation, shifting toward sustainable food consumption and production is a priority. In this context, the EAT-Lancet diet was developed by combining health and Earth's carrying capacity at the same time, allowing for cultural, context and individual preferences.
Comparing the EAT-Lancet recommendations to current global consumption, it appears that high-income countries largely overconsume red meat, which is associated with great environmental impacts, while proteins from plant-based sources are neglected. Therefore, shifting towards a diet with less red meat and more legumes is often recommended to reduce one's environmental footprint. In parallel, redistributing livestock subsidies to plant-based crops is often seen as necessary for a shift towards sustainable consumption. However, environmental assessments of diets often omit market effects, taking consumption rather than production as a starting point. Moreover, the current literature on instruments for environmentally sustainable food systems does not compare to any benchmarks representing the amplitude of changes needed. Consequently, a complete analysis of on one side, the potential for environmental impact reduction from adopting the EAT-Lancet diet and on the other side, the potential from public policy instruments to reach such a diet is currently lacking. This thesis aims to fill this gap by answering the following research question: Shifting towards the EAT-Lancet diet and lowering environmental impacts: two sides of the same coin? To answer this question, we assessed, in the first part, the mitigation potential of several diet shifts and, in the second part, the potential of financial and regulatory instruments to achieve a sustainable food system.
In the first part, we defined and assessed the environmental consequences of various dietary shift scenarios towards the EAT-Lancet recommendations for red meat and legumes. In Chapter 3, we evaluated a hypothetical scenario of a diet shift in the EU. For this purpose, we combined an agro-economic model, CAPRI, with a consequential life cycle assessment. In Chapter 4, we assessed three additional scenarios in the EU, the EU and China, 40% of the largest red meat eaters and the whole world, using the same methodology. The results show that the environmental benefits from individual consumption changes are limited by the structure of our global economy. Indeed, the global demand for red meat drives changes in agricultural production, which is thus only slightly affected. However, when 40% of the world's population is shifting diets, almost as many environmental benefits as when the whole world shifts diets could be obtained compared with a business-as-usual scenario. These benefits are apparent through the reduction in acidification, eutrophication, and greenhouse gasses and particulate matter emissions, particularly in countries specialised in livestock production. The associated decrease in feed production, which is greater than the increase in legume production, would decrease the impacts on freshwater ecotoxicity and eutrophication and lower the pressure on resource use.
In the second part, the effectiveness of several public policy instruments to shift eating patterns and mitigate environmental impacts are evaluated. Chapter 5 focusses on financial and regulatory instruments. The current literature is analysed and reported consumption changes are compared with the EAT-Lancet diet. Similarly, reported greenhouse gas emission changes are compared with three climate benchmarks representative of what is needed for a sustainable food system. Other potential environmental impacts are estimated on the basis of reported changes in agricultural production. Among the instruments analysed, only an unthinkable consumer price change could lead to the targeted food consumption with the least trade-offs in terms of environmental impacts but with further widening social injustice. The results of this analysis show that the current instrument designs fail to achieve a sustainable diet and comfort the status quo.
To conclude, the results show that shifting to a sustainable diet means shifting the current efficiency paradigm to a sufficiency paradigm. There are no one-size-fits-all solutions for this shift, and both top-down and bottom-up approaches should be considered together to mutually reinforce each other. Finally, including all sustainability aspects through transdisciplinary research as well as putting our imagination at work is essential for defining coherent context-specific solutions. This multi-approach should ensure that the path of a food systems transformation is taken.status: Publishe
Vliegen, schimmels en microbiële functies: de rol van micro-organismen bij de productie van de zwarte soldatenvlieg (Hermetia illucens) en bij het verbeteren van het larvale nutritioneel profiel
No full textThe Black soldier fly (Hermetia illucens L., Diptera: Stratiomyidae) is an insect produced on an industrial scale, mainly as a feed ingredient. The nutritional profile of black soldier fly larvae (BSFL) make them a suitable, alternative protein source in various animal feeds, however their fatty acid profile lacks several polyunsaturated fatty acids, specifically ω-3 and ω-6 fatty acids, which limits the application of BSFL as an ingredient in fish feed. The nutritional profile of the larvae is influenced by their diet, and the BSFL can be reared on a range of substrates, including various waste streams such as restaurant waste, agricultural side-products and animal manure, reducing waste through the bioconversion of these waste streams into valuable insect biomass. However, the role of the insect's microbiome during the conversion of these waste streams and potential functions they have during BSFL development, remain poorly understood.
This PhD project focusses on two aspects involving microorganisms and the BSFL. First, this project investigates the potential to improve the fatty acid profile of the BSFL through substrate manipulation, using the oil-producing fungus Mortierella alpina as a cheap and sustainable source of ω-3 and ω-6 fatty acids. Here, nutritionally-poor agricultural sidestreams will be fermented with this microorganism and the fermented substrates will be developed into a nutritional BSFL feed. In the second part of the PhD, advance DNA sequencing techniques will be employed to identify the BSFL microbiota, a collection of bacteria, fungi and viruses that inhabit the larvae, in order to discover potential metabolic and protective microbial functions they provide for their host, potentially aiding the BSFL to grown on a wide variety of substrates. Identification of these microorganisms and their potential beneficial functions for the BSFL can further our understanding of the role of the insect microbiome and potentially identify bacterial- and/or fungal species suited as probiotics.status: Publishe