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Tenosynovial giant cell tumor (TGCT) is a rare type of tumor that originates from the synovium of joints and tendon sheaths. It is characterized by recurring genetic abnormalities, often involving the CSF1 gene. Common symptoms include pain and swelling, which are not specific to TGCT, so MRI and a pathological biopsy are needed for an accurate diagnosis. We report the case of a 45-year-old man who experienced painful swelling in his right hip for six months. Initially, this was diagnosed as Erdheim-Chester disease. However, whole exome sequencing (WES) and RNA-Sequencing revealed a CSF1::GAPDHP64 fusion, leading to a revised diagnosis of TGCT. The patient was treated with pegylated interferon and imatinib, which resulted in stable disease after three months. Single-cell transcriptome analysis identified seven distinct cell clusters, revealing that neoplastic cells expressing CSF1 attract macrophages. Analysis of ligand-receptor interactions showed significant communication between neoplastic cells and macrophages mediated by CSF1 and CSF1R. Our findings emphasize the importance of comprehensive molecular analysis in diagnosing and treating rare malignancies like TGCT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Fähnrich, Gasimova, Maluje, Ott, Sievert, Fliedner, Reimer, Künstner, Gebauer, Kebenko, von Bubnoff, Kirfel, Sailer, Röcken, Konukiewitz, Klapper, Frydrychowicz, Mogadas, Huebner, Busch and Khandanpour.)

Positive and negative ions produced by radioactive sources and corona discharges in gases find a number of applications, including charging aerosol particles prior to their measurement by electrical and/or electrical mobility techniques. The degree to which these ions can charge aerosol particles depends on their mobility and mass; properties that are strongly affected by the composition of the carrier gas and the impurities that it contains. We show that when the purity of the carrier gas is increased, the mobility of both positive and negative ions increases by more than 50%, whereas the respective masses reduce by more than 50%. In most cases, the dominant positive species is N 4 + , whereas NO 2 - and NO 3 - prevail for the negative polarity. Differences in ion mobility and mass resulting from the two ionization methods (i.e., radioactive source and corona discharges) remain limited. When volatile methyl siloxanes (VMS) are introduced deliberately to the gas, the mobility of the cations decreases by 39% and their mass increases by 385%, while the dominant mobility and mass peaks of the negative ions remains almost unaffected. Interestingly, introduction of VMS also leads to consistent and reproducible positive ion properties across all variations of the experiments, which can be especially relevant for charging aerosol particles in a reproducible manner. Taken together, the new measurements we report in this paper corroborate prior knowledge that the composition and purity of the carrier gas strongly influence the properties of positive and negative ions generated in aerosol neutralizers, and provide new evidence regarding their evolution in the presence of impurities.

Dystonia due to pathogenic variants in the THAP1 gene (DYT-THAP1) shows variable expressivity and reduced penetrance of ~ 50%. Since THAP1 encodes a transcription factor, modifiers influencing this variability likely operate at the gene expression level. This study aimed to assess the transferability of differentially expressed genes (DEGs) in neuronal cells related to pathogenic variants in the THAP1 gene, which were previously identified by transcriptome analyses. For this, we performed quantitative (qPCR) and Digital PCR (dPCR) in cultured fibroblasts. RNA was extracted from THAP1 manifesting (MMCs) and non-manifesting mutation carriers (NMCs) as well as from healthy controls. The expression profiles of ten of 14 known neuronal DEGs demonstrated differences in fibroblasts between these three groups. This included transcription factors and targets (ATF4, CLN3, EIF2A, RRM1, YY1), genes involved in G protein-coupled receptor signaling (BDKRB2, LPAR1), and a gene linked to apoptosis and DNA replication/repair (CRADD), which all showed higher expression levels in MMCs and NMCs than in controls. Moreover, the analysis of genes linked to neurological disorders (STXBP1, TOR1A) unveiled differences in expression patterns between MMCs and controls. Notably, the genes CUEDC2, DRD4, ECH1, and SIX2 were not statistically significantly differentially expressed in fibroblast cultures. With > 70% of the tested genes being DEGs also in fibroblasts, fibroblasts seem to be a suitable model for DYT-THAP1 research despite some restrictions. Furthermore, at least some of these DEGs may potentially also serve as biomarkers of DYT-THAP1 and influence its penetrance and expressivity., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Pathogenic variants in several genes have been linked to genetic forms of isolated or combined dystonia. The phenotypic and genetic spectrum and the frequency of pathogenic variants in these genes have not yet been fully elucidated, neither in patients with dystonia nor with other, sometimes co-occurring movement disorders such as Parkinson's disease (PD)., Objectives: To screen >2000 patients with dystonia or PD for rare variants in known dystonia-causing genes., Methods: We screened 1207 dystonia patients from Germany (DysTract consortium), Spain, and South Korea, and 1036 PD patients from Germany for pathogenic variants using a next-generation sequencing gene panel. The impact on DNA methylation of KMT2B variants was evaluated by analyzing the gene's characteristic episignature., Results: We identified 171 carriers (109 with dystonia [9.0%]; 62 with PD [6.0%]) of 131 rare variants (minor allele frequency <0.005). A total of 52 patients (48 dystonia [4.0%]; four PD [0.4%, all with GCH1 variants]) carried 33 different (likely) pathogenic variants, of which 17 were not previously reported. Pathogenic biallelic variants in PRKRA were not found. Episignature analysis of 48 KMT2B variants revealed that only two of these should be considered (likely) pathogenic., Conclusion: This study confirms pathogenic variants in GCH1, GNAL, KMT2B, SGCE, THAP1, and TOR1A as relevant causes in dystonia and expands the mutational spectrum. Of note, likely pathogenic variants only in GCH1 were also found among PD patients. For DYT-KMT2B, the recently described episignature served as a reliable readout to determine the functional effect of newly identified variants. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Cellular electron cryo-tomography (cryoET) produces high-resolution three-dimensional images of subcellular structures in a near-native frozen-hydrated state. These three-dimensional images are obtained by recording a series of two-dimensional tilt images on a transmission electron cryo-microscope that are subsequently back-projected to form a tomogram. Key to a successful experiment is however a high-quality sample. This chapter outlines a basic workflow for the preparation of cellular cryoET samples. It covers the preparation of infected cells on electron cryo-microscopy grids and the vitrification by plunge-freezing and clipping of grids into AutoGrid rims. It also provides a general overview of the workflow for thinning the vitrified cells by focused ion beam (FIB) milling. Although this book is dedicated to Rift Valley fever virus research, the present protocol may also be applied to any other research subject where high-resolution structural insight into intracellular processes is desired., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)