De vraag die in deze Openbare Les centraal staat is hoe internetcultuur een duurzame grondslag gegeven kan worden, aan gene zijde van hype en speculatie. De toekomst is immers aangebroken en het tijdperk van de inleidingen ligt achter ons. Nu de ‘nieuwe media’ algemeen verspreid zijn, gaat het niet langer om de vraag hoe deze cultuurtechnieken werken, maar om wat ermee gedaan kan worden, en wie het voor het zeggen heeft binnen de netwerkarchitectuur. Dit roept belangrijke vragen op, zoals: Wie heeft toegang tot welke kennis? Hoe wordt er omgegaan met conflict? Wat is de invloed van gebruikers? Wat betekent de opkomst van niet-westerse landen zoals India, China en Brazilië voor de internetcultuur in het algemeen? Kan de claim dat cultuur en creativiteit de rol overnemen van de computeringenieurs wel waargemaakt worden en wat is de economische grondslag van deze ‘creatieve industrie’? Wordt het networking, of notworking?
Hyperhomocysteinemia is a risk factor for cardiovascular disease, neurological disorders, and bone abnormalities. The key enzyme in homocysteine metabolism, cystathionine-β-synthase (CBS) is recognized as a target for new homocysteine-lowering therapies including enzyme replacement and gene therapy. Currently, there are no pharmacotherapies available that enhance CBS activity through its allosteric mechanism. The only known allosteric activator of CBS is S-adenosyl-L-methionine (SAM), which is available as a food supplement, but its effectiveness is limited by low membrane permeability and universal involvement in methylation reactions as a substrate. The discovery of CBS activators in high-throughput screening is challenging due to a lack of dedicated assays. Available HTS-compatible activity assays for CBS rely on measuring the product hydrogen sulfide or methanethiol where the signal increases with increased CBS activity. In the case of fluorescence-based assays, it is challenging to discern activators from autofluorescent compounds. In this study, we introduce a homocysteine consumption assay for isolated human CBS (HconCBS) based on the absorbance of Ellman's reagent. This assay leverages a decrease in signal upon CBS activation, with performance parameters exceeding the requirements for high-throughput screening. In a commercial library of 3010 compounds, the HconCBS assay identified 10 hit compounds as more active than SAM, whereas a fluorescence-based assay using 7-azido-4-methylcoumarin (AzMC) identified 141 hits. HconCBS identified 101 compounds with autoabsorbance which did not include hit compounds, while the fluorescence-based assay identified 383 autofluorescent compounds which included all hit compounds. While 4 out of 10 HconCBS hits were confirmed when purchased from a new source, the compounds affected homocysteine rather than CBS. Nevertheless, HconCBS consistently detected the CBS activator seleno-adenosyl-L-methionine (SeAM) added to 4 library plates and re-discovered the same library hits in 3 out of 4 re-screened plates. Taken together, HconCBS was designed to enable the discovery of allosteric CBS activators with greater reliability than fluorescence-based methods. Despite identifying some compounds that acted on homocysteine rather than CBS, the assay consistently identified the CBS activators SAM and SeAM and demonstrated reproducibility across two screening rounds. These findings establish HconCBS as a valuable tool for identifying potential therapeutic candidates for hyperhomocysteinemia, addressing a key gap in the development of CBS-targeted pharmacotherapies.
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We tested the hypothesis that in human ageing a decreased intramuscular acylcarnitine status is associated with (pre-)frailty, reduced physical performance and altered mitochondrial function. Results showed that intramuscular total carnitine levels and acetylcarnitine levels were lower in (pre-)frail old females compared to fit old females and young females, whereas no differences were observed in males. The low intramuscular acetylcarnitine levels in females correlated with low physical performance, even after correction for muscle mass (%), and were accompanied with lowered expression of genes involved in mitochondrial energy production and functionality. We concluded that in (pre-)frail old females, intramuscular total carnitine levels and acetylcarnitine levels are decreased, and this decrease is associated with reduced physical performance and low expression of a wide range of genes critical for mitochondrial function. The results stress the importance of taking sex differences into account in ageing research.
MULTIFILE
Physical rehabilitation programs revolve around the repetitive execution of exercises since it has been proven to lead to better rehabilitation results. Although beginning the motor (re)learning process early is paramount to obtain good recovery outcomes, patients do not normally see/experience any short-term improvement, which has a toll on their motivation. Therefore, patients find it difficult to stay engaged in seemingly mundane exercises, not only in terms of adhering to the rehabilitation program, but also in terms of proper execution of the movements. One way in which this motivation problem has been tackled is to employ games in the rehabilitation process. These games are designed to reward patients for performing the exercises correctly or regularly. The rewards can take many forms, for instance providing an experience that is engaging (fun), one that is aesthetically pleasing (appealing visual and aural feedback), or one that employs gamification elements such as points, badges, or achievements. However, even though some of these serious game systems are designed together with physiotherapists and with the patients’ needs in mind, many of them end up not being used consistently during physical rehabilitation past the first few sessions (i.e. novelty effect). Thus, in this project, we aim to 1) Identify, by means of literature reviews, focus groups, and interviews with the involved stakeholders, why this is happening, 2) Develop a set of guidelines for the successful deployment of serious games for rehabilitation, and 3) Develop an initial implementation process and ideas for potential serious games. In a follow-up application, we intend to build on this knowledge and apply it in the design of a (set of) serious game for rehabilitation to be deployed at one of the partners centers and conduct a longitudinal evaluation to measure the success of the application of the deployment guidelines.
De wijkverpleging staat voor grote uitdagingen. Meer ouderen met gezondheidsproblemen wonen tot hoge leeftijd thuis. Toch is er weinig bekend over welke uitkomsten belangrijk zijn in de wijkverpleging en hoe deze gebruikt kunnen worden voor leren en verbeteren.
Electrohydrodynamic Atomization (EHDA), also known as Electrospray (ES), is a technology which uses strong electric fields to manipulate liquid atomization. Among many other areas, electrospray is used as an important tool for biomedical application (droplet encapsulation), water technology (thermal desalination and metal recovery) and material sciences (nanofibers and nano spheres fabrication, metal recovery, selective membranes and batteries). A complete review about the particularities of this tool and its application was recently published (2018), as an especial edition of the Journal of Aerosol Sciences. One of the main known bottlenecks of this technique, it is the fact that the necessary strong electric fields create a risk for electric discharges. Such discharges destabilize the process but can also be an explosion risk depending on the application. The goal of this project is to develop a reliable tool to prevent discharges in electrospray applications.
