Computer-supported laboratory for production-oriented electrotechnical systems

At the electrical engineering department of the K.U.Leuven an education research project was started in October 1997. The target is to develop a powerful environment to teach students to solve practice-oriented problems as they will encounter them in industry furtheron in their career. In order to give a wide use to the developed environment, a close collaboration has been established with three polytechnical engineering institutes. Self-dependence has to be stimulated by creating possibilities for real “hands-on experience”. Such an educational environment implicates time-problems, high investment costs and last but not least safety restrictions. The project contributes to the solution of these problems by using simulation- and softwareenvironments, without loosing the real hands-on feeling

Longitudinal study on the association between three dietary indices, anthropometric parameters and blood lipids

Background: From a health promotion perspective, the use of dietary indices is preferred above single nutrients and foods to evaluate diet quality. Longitudinal research about the association between dietary indices and respectively anthropometric parameters and blood lipids is lacking. The aim of this study was to investigate the longitudinal association between three dietary indices (Healthy Eating Index-2010 (HEI), Mediterranean Diet Score (MDS) and Diet Quality Index (DQI)) and respectively anthropometric parameters and blood lipids. Methods: A three day diet record was completed by 373 men and 197 women in 2002-2004 and 2012-2014. HEI, MDS and DQI were calculated. Waist circumference (WC) and Body Mass Index (BMI) were used as anthropometric parameters. A linear regression analysis was performed to investigate associations between changes in dietary indices and changes in respectively anthropometric parameters and blood lipids, adjusted for potential confounders. Results: Only in men an increase in all three dietary indices was associated with a decrease in WC and BMI in the non-adjusted analysis and for HEI and DQI also in the adjusted analysis. No longitudinal associations were found between dietary indices and blood lipids both in men and women. Conclusions: Only few associations were found between dietary indices and anthropometric parameters, whilst no associations were found with blood lipids. An increase in dietary indices was associated with an improvement in anthropometric parameters only in men. As this is the first study investigating associations between changes in dietary indices and changes in respectively anthropometric parameters and blood lipids, further research is needed to evaluate these possible associations

Biofluid Markers for Prodromal Parkinson's Disease:Evidence From a Catecholaminergic Perspective

Parkinson's disease (PD) is the most frequent of all Lewy body diseases, a family of progressive neurodegenerative disorders characterized by intra-neuronal cytoplasmic inclusions of α-synuclein. Its most defining features are bradykinesia, tremor, rigidity and postural instability. By the time PD manifests with motor signs, 70% of dopaminergic midbrain neurons are lost, and the disease is already in the middle or late stage. However, there are various non-motor symptoms occurring up to 20 years before the actual parkinsonism that are closely associated with profound deficiency of myocardial noradrenaline content and peripheral sympathetic denervation, as evidenced by neuroimaging experiments in recent years. Additionally, there is an inherent autotoxicity of catecholamines in the neuronal cells in which they are produced, forming toxic catecholaldehyde intermediates that make α-synuclein prone to aggregation, initiating a cascade of events that ultimately leads to neuronal death. The etiopathogenesis of PD and related synucleinopathies thus may well be a prototypical example of a catecholamine-regulated neurodegeneration, given that the synucleinopathy in PD spreads in synergy with central and peripheral catecholaminergic dysfunction from the earliest phases onward. That is why catecholamines and their metabolites, precursors, or derivatives in cerebrospinal fluid or plasma could be of particular interest as biomarkers for prodromal and de novo PD. Because there is great demand for such markers, this mini-review summarizes all catecholamine-related studies to date, in addition to providing profound neurochemical evidence on a systemic and cellular level to further emphasize this hypothesis and with emphasis on extracellular vesicles as a novel diagnostic and therapeutic incentive

Cross-sectional study on the relationship between the Mediterranean Diet Score and blood lipids

Background: Blood lipids are cardiovascular health indicators. High LDL cholesterol values and/or high total cholesterol (TC)/HDL cholesterol ratios are positively related with cardiovascular mortality. Evidence suggests that a Mediterranean diet can reduce the incidence of cardiovascular diseases. Adherence to the Mediterranean diet is often measured by the Mediterranean Diet Score (MDS). However, the association between the Mediterranean diet and blood lipid profiles seems still inconclusive. The aim of this study was to investigate the relationship between the MDS, its different components and blood lipid profiles. Methods: A sample of 506 women and 707 men (aged 18-75 years) was recruited. Three-day diet records were used to calculate the MDS. Blood samples were analyzed for serum TC, LDL and HDL cholesterol. ANOVA was used to analyze blood lipids across the MDS tertiles. A multivariate linear regression analysis was performed to investigate the associations between the MDS, its components and blood lipids, adjusted for several confounders. All analyses were stratified by gender. Results: Few gender-specific associations were found between the MDS, its components and blood lipids. Only in men, the total MDS was negatively related with LDL cholesterol and the ratio TC/HDL cholesterol while positively with HDL cholesterol. In women, respectively two (MUFA/SFA and cereals) and in men three (fruits & nuts, meat and alcohol) of the nine MDS components were related with blood lipids. Conclusions: Analyses investigating the relationship between the MDS, its components and blood lipid profiles indicate only limited influence of the Mediterranean diet on blood lipids. More associations were detected in men compared to women

Onchocerciasis-associated epilepsy: an explorative case-control study with viral metagenomic analyses on Onchocerca volvulus [version 2; peer review: 2 approved]

Background A high prevalence of onchocerciasis-associated epilepsy (OAE) has been observed in onchocerciasis-endemic areas with high ongoing Onchocerca volvulus transmission. However, the pathogenesis of OAE remains to be elucidated. We hypothesise that the O. volvulus virome could be involved in inducing epilepsy. With this study, we aim to describe the O. volvulus virome and identify potential neurotropic viruses linked to OAE. Methods In Maridi County, an onchocerciasis endemic area in South Sudan with a high prevalence of OAE, we will conduct an exploratory case-control study enrolling 40 persons aged 12 years and above with palpable onchocerciasis nodules. Cases will be participants with OAE (n=20), who will be age- and village-matched with controls without epilepsy (n=20). For each study participant, two skin snips at the iliac crest will be obtained to collect O. volvulus microfilariae, and one nodulectomy will be performed to obtain adult worms. A viral metagenomic study will be conducted on microfilariae and adult worms, and the O. volvulus virome of persons with and without OAE will be compared. The number, size, and localisation of onchocerciasis nodules in persons with and without OAE will be described. Moreover, the pre- and post-nodulectomy frequency of seizures in persons with OAE will be compared. Ethics and dissemination The protocol has been approved by the Ethics Committee of the University of Antwerp and the Ministry of Health of South Sudan. Findings will be disseminated nationally and internationally via meetings and peer-reviewed publications. Registration ClinicalTrials.gov registration NCT05868551 (https://clinicaltrials.gov/study/NCT05868551). Protocol version 1.1, dated 09/05/2023

Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points

G-proteïne gekoppelde receptoren in de model organismen drosophila melanogaster en caenorhabditis elegans.

G-proteïne gekoppelde receptoren (GPCRs) zijn vandaag de belangrijkste g roep van doelwitmoleculen voor de farmaceutische industrie. Daarom is en blijft de identificatie en karakertisatie van GPCRs één van de hoo fddoelen van wetenschappelijk onderzoek in de industie en in vele academ ische instellingen. Neuropeptide GPCRs vertegenwoordigen de grootste en belangrijkste groep van GPCRs omdat neuropeptiden bij vele invertebraten (zoals C. e legans) de meest prominente neurotransmitters zijn. Ze zijn bet rokken bij vele biologische processen zoals gedrag, de immuun resp ons en/of neuroendocriene systemen. Drosophila melanogaster en Caenorhabditis elegans zijn twee veel gebruikte modelorganismen omdat hun genoom reeds gepubliceerd is. Het Drosophila genoom codeert voor 54 neuropeptide GPCRs, waarvan er reeds 26 gekarakteriseerd zijn. De eerste Drosophila receptor, beschreven in deze doctoraatsstudie, is betrokken in de regulatie van biologische ritmen. De receptor kan geactiveerd worden door pigment dispersing factor (PDF), een neuropeptide dat gesynthetis eerd wordt in de ventrolaterale neuronen (LNv). Vliegen die geen functio neel PDF peptide bevatten, vertonen abnormale bewegingen in dag-nacht ri tmen en een verandering in hun geotactische respons. De insect PDF recep tor vertoont het meeste gelijkenis met calcitonine- en CGRP-receptoren b ij zoogdieren. Wanneer de PDF-R tot expressie gebracht wordt in HEK-293 cellen, stijgt bij activatie het cAMP gehalte, en minder duidelijk ook h et calcium gehalte in de cellen. Co-transfectie met NF-1 verbetert duide lijk de koppeling van de receptor aan adenylaat cyclase. PDF-R</ &gt; mutanten vertonen fenotypes die vergelijkbaar zijn met deze van de&amp;nbs p;PDF mutanten zelf: veranderingen in geotactisch gedrag en een ve rhoogde a-ritmiciteit, een duidelijke aanwijzijng dat de PDR-R betrokken is bij de PDF signaaltransductie. De PDF-R komt tot expressie in divers e groepen neuronen in het centraal zenuwstelsel die maar een klein aanta l pacemaker neuronen bevatten. Er zijn ook aanwijzingen dat FMRFamiden, aanwezig in de lamina van de op tische lob van de vlieg, een rol zouden spelen bij de regulatie van circ adiane ritmen. Daarom kloneerden we ook verschillende mogelijke FMRFamid e-gelijkende receptoren bij Drosophila en Caenorhabdi tis. We identificeerden CG7395 als het gen dat de short ne uropeptide F receptor (sNPF) codeert bij Drosophila. sNPFs be horen tot de familie van de FMRFamide-gerelateerde peptiden (FaRPs) en z ijn betrokken bij voedsel-inname en lichaamsgewicht. Een mogelijke rol i n de regulatie van biologische ritmen is nog niet aangetoond. De sNPF-R vertoont de grootste homologie met de vertebrate NPY-receptoren en wanne er de receptor tot expressie gebracht wordt in CHO-cellen, kan deze enke l gectiveerd worden door de vier Drosophila sNPF peptiden. De receptor komt tot expressie in een klein aantal neuronen in zowel het p erifeer, als het centraal zenuwstelsel van embryo s en volwassenen. Het C. elegans genoom codeert voor meer dan 60 Famide-gelijke nde peptiden. Ze worden gecodeerd door de zogenaamde flp-gene n. Het is dan ook een grote uitdaging om al deze peptiden te koppelen aa n hun mogelijke receptoren, die waarschijnlijk behoren tot de groep van meer dan 130 neuropeptide GPCRs die voorspeld zijn in het C. ele gans genoom. We zijn erin geslaagd om dit doel te bereiken voor drie C. elega ns receptoren. De eerste receptor wordt gecodeerd door gen C26F1.6 en wordt geactiveerd door twee synthetische peptiden die eindigen in M(ofL )VRFamide. Een farmacologisch profiel van het meest actieve peptide toon t echter aan dat de meest actieve sequentie SMVRFamide is. Aangezien het voorspelde peptide nog niet biochemisch kon geïsoleerd kon worden, blij ft het voorlopig onduidelijk welk endogeen peptide het biologisch actiev e is. RNAi studies tonen aan dat de receptor verwikkeld is in de regulat ie van de voortplanting. Het expressie patroon de receptor wordt enkel terug gevonden in enkele cellen in het L3 en L4 stadium komt overeen met de vooropgestelde functie. De tweede gekarakteriseerde receptor word t gecodeerd door het gen Y59H11AL.1 en kan geactiveerd worden door een h ele reeks peptiden die gecodeerd worden door verschillende flp</ &gt; genen. Het meest actieve peptide is SPMERSAMVRFamide. De functie van d e receptor en de liganden is tot nog toe onduidelijk, maar aangezien de receptor behoort tot de familie van tachykinine-verwante receptoren, zou deze motorische functies kunnen hebben. De derde gekarakteriseerde rece ptor heeft twee splice varianten (a en b). Splice variant b is dertig am inozuren langer aan de intracelluliare C-terminale zijde, wat kan implic eren dat er een verschil zou zijn in de koppeling met de G-proteïnen. Be ide receptoren gebruiken echter de Gaq signaaltransductieweg in zoogdier cellen. Beide receptoren worden ook geactiveerd door twee peptiden, die gecodeerd worden door het flp-2 gen (FLP-2A en FLP-2B). Een f armacologisch profiel toont aan dat EPIRFamide de minimum sequentie is d ie nodig is voor activiteit. Vele C. elegans receptoren konden echter niet gekarakteriseer d worden gebruik makende van een bibliotheek van synthetische peptiden. Daarom werden er ook biologische extracten aangemaakt waarmee de restere nde receptoren werden gescreend. Dit bleek echter niet de gehoopte resul taten op te leveren. We hopen echter in de toekomst toch nog vele van de weesreceptoren te karakteriseren door enerzijds onze synthetische pepti denbibliotheek nog verder uit te bouwen en anderzijds door nieuwe extrac ten te maken. We kunnen tot slot toch stellen dat door de resultaten van het werk besc hreven in deze thesis vele nieuwe wegen kunnen onderzocht worden die kun nen leiden tot de verdere opheldering van biologische processen zoals bi ologische ritmen bij Drosophila en Caenorhabditis. Hopelijk kunnen de toekomstige experimenten ook nieuw acpecten blootleg gen die betrokken zijn bij deze belangrijke processen, zowel bij inverte braten als bij vertebraten.Chapter 1: General introduction: G-protein coupled receptors 1 Chapter 2: Characterization of orphan G-protein coupled receptors 13 Chapter 3: Characterization of the Drosophila PDF-receptor involved in biological rhythms 32 Chapter 4: Characterization of the short neuropeptide F receptor in Drosophila 58 Chapter 5: RFamide related peptide receptors in C. elegans: characterization of the C26F1.6 and the Y59H11AL.1 and T19F4.1 receptors 80 Chapter 6: General discussion and future prospects 133 Summary 142 Samenvatting 145 Reference list 148status: publishe