Translocator protein is a marker of activated microglia in rodent models but not human neurodegenerative diseases

Microglial activation plays central roles in neuroinflammatory and neurodegenerative diseases. Positron emission tomography (PET) targeting 18 kDa Translocator Protein (TSPO) is widely used for localising inflammation in vivo, but its quantitative interpretation remains uncertain. We show that TSPO expression increases in activated microglia in mouse brain disease models but does not change in a non-human primate disease model or in common neurodegenerative and neuroinflammatory human diseases. We describe genetic divergence in the TSPO gene promoter, consistent with the hypothesis that the increase in TSPO expression in activated myeloid cells depends on the transcription factor AP1 and is unique to a subset of rodent species within the Muroidea superfamily. Finally, we identify LCP2 and TFEC as potential markers of microglial activation in humans. These data emphasise that TSPO expression in human myeloid cells is related to different phenomena than in mice, and that TSPO-PET signals in humans reflect the density of inflammatory cells rather than activation state.Published versionThe authors thank the UK MS Society for financial support (grant number: C008-16.1). DRO was funded by an MRC Clinician Scientist Award (MR/N008219/1). P.M.M. acknowledges generous support from Edmond J Safra Foundation and Lily Safra, the NIHR Senior Investigator programme and the UK Dementia Research Institute which receives its funding from DRI Ltd., funded by the UK Medical Research Council, Alzheimer’s Society, and Alzheimer’s Research UK. P.M.M. and D.R.O. thank the Imperial College Healthcare Trust-NIHR Biomedical Research Centre for infrastructure support and the Medical Research Council for support of TSPO studies (MR/N016343/1). E.A. was supported by the ALS Stichting (grant “The Dutch ALS Tissue Bank”). P.M. and B.B.T. are funded by the Swiss National Science Foundation (projects 320030_184713 and 310030_212322, respectively). S.T. was supported by an “Early Postdoc.Mobility” scholarship (P2GEP3_191446) from the Swiss National Science Foundation, a “Clinical Medicine Plus” scholarship from the Prof Dr. Max Cloëtta Foundation (Zurich, Switzerland), from the Jean et Madeleine Vachoux Foundation (Geneva, Switzerland) and from the University Hospitals of Geneva. This work was funded by NIH grants U01AG061356 (De Jager/Bennett), RF1AG057473 (De Jager/Bennett), and U01AG046152 (De Jager/Bennett) as part of the AMP-AD consortium, as well as NIH grants R01AG066831 (Menon) and U01AG072572 (De Jager/St George-Hyslop)

Assessing agro-ecological practices using a combination of three sustainability assessment tools

This paper is based on results from the research project UNISECO, which is funded by European Union’s Horizon 2020 research and innovation programme under grant agreement No. 773901.We would like to thank all the farmers, farm organisations and stakeholders of the multi-actor platforms of the UNISECO project who contributed to the data collection. We also like to thank Andreas Basler whose corrections improved the comprehensibility of the paper.Peer reviewedPublisher PD

Determining the role of FoF1-ATP synthase dimers in Trypanosoma brucei mitochondrial biogenesis

ATP synthase dimers have previously been identified to be major determinants of mitochondrial cristae ultrastructure. In order to determine the role of these dimers in the organellar architecture of Trypanosoma brucei, we performed a functional screen that identified a single T. brucei ATP synthase subunit that, upon depletion, destabilizes primarily dimers of the enzyme without disrupting the singular functional unit

VRodel - A virtual sledding simulator

Introduction & Purpose Sledding is a low-cost and accessible recreational activity popular in alpine regions. However, the risk of injury is high, especially for beginners or tourists, according to the Österreichisches Kuratorium für Alpine Sicherheit (2021). Therefore, promoting sledding safety is important to minimize the number of accidents and fatalities in the sport. Sterr (2019) says, the major reason behind an accident is often the lack of skill in steering the sled. Hence, it would be ideal to acquire the skill to steer before going on a track. In many fields skill training is done in virtual reality. Realism in skill training is a major aspect in the virtual worlds according to Newman et al. (2022). Therefore, the goal of VRodel was to create a virtual environment for training that is as close as reasonably possible to reality. Methods In the first step, an environment had to be chosen that would be safe yet effective for training the skill of steering the sled. Next, the sledding track of Kühtai was transferred to a virtual model by means of drone based photogrammetry. The three-dimensional model was then cleaned, polished, and set into the virtual valley that surrounds the track. In a third step, a game was developed in the virtual world to create a virtual training experience. Input from professional sledders and comparisons to time splits of the real track were used to adapt the physics. The user steers the sled by moving their hands in space to reflect the pulling of the reins and leaning into curves. To increase immersion, the safety training uses gamification aspects. As a fourth step, the game was tested by four experts from Rodel Austria and 49 beta-testers, which gave feedback about the realism. Results The project resulted in a virtual reality safety training for the sport of sledding, that excels the current sledding simulation games in terms of appearance and realism. This was underlined by the feedback from the experts of the Austrian Luge Federation and the beta-testers that gave the simulation an average score of 4.98 out on a scale from 1 to 7. In Figure 1, a glimpse of the virtual world is visible. Discussion Le Noury et al. (2022) mention the potential of extended reality for training a skill in sports in their review. They also outlined that this field showed low efficacy on improving motor skills in the past and more research is needed. This project is addressing the needs of society for safer luging and at the same time uses an approach that needs more research according to Le Noury et al. (2022). Therefore, not only the project’s goals have been met, but also a contribution to the scientific progress in this field was made. Conclusion The immersive nature of the VRodel training program successfully engaged users, particularly children, through its gamified elements. Furthermore, this initiative not only enables sledding on a virtual track but also enables a study on the efficacy of virtual skill training in sledding. References: Le Noury, P., Polman, R., Malone, M., & Gorman, A. (2022). A narrative review of the current state of extended reality technology and how it can be utilised in sport. Sports Medicine, 52, 1473–1489. https://doi.org/10.1007/s40279-022-01669-0 Newman, M., Gatersleben, B., Wyles, K., & Ratcliffe, E. (2022). The use of virtual reality in environment experiences and the importance of realism. Journal of Environmental Psychology, 79, Article 101733. https://doi.org/10.1016/j.jenvp.2021.101733 Österreichisches Kuratorium für Alpine Sicherheit (2021). Der Zwischenbericht Winter 2021/22 liegt vor: 111 Alpintote in Österreichs Bergen (Mittel 10 Jahre: 113). Insgesamt verunfallten 6.716 Personen in Österreich. Die alpinen Unfallzahlen nehmen im Vergleich zum Vorwinter (2.476 Verunfallte) und dem langjährigen Mittel wieder Fahrt auf (Mittel 10 Jahre: 7.242) [The Winter 2021/22 interim Report is available: 111 Alpine fatalities in Austria‘s mountains (average 10 years: 113). A total of 6,716 people had an accident in Austria. Compared to the previous winter (2,476 accidents) and the long-term average (10-year average: 7,242), the number of alpine accidents is picking up again.]. https://alpinesicherheit.at/wp-content/uploads/2022/05/PA-2022-Winter-2021_22_12042022.pdf Sterr, R. (2019). Rodeln in Zahlen [Sledging in numbers]. ÖKAS, Österreichisches Kuratorium für Alpine Sicherheit. https://www.alpinmesse.info/de/Rodeln-in-Zahlen

A case study for detection and modelling of submerged deadwood from UAV-borne topo-bathymetric LiDAR point clouds

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