Biology subjects

Steiner, L.

Publications and source records attributed to Steiner, L..

6 recordsLinked to original sources

bioRxiv2026

The metabolic profile of Extracellular Vesicles identifies and separates patients with Sarcoidosis and Anti-Synthetase Syndrome

Sarcoidosis is a multisystem disorder that primarily affects the lungs and is characterizedby granulomatous inflammation. However, much of the underlying disease mechanisms remain poorly understood. Extracellular vesicles (EVs) are small membrane-bound particles released by all cells and carry various cargos including metabolites. They are involved in intercellular communication that can be dysregulated in diseases.This study characterizes the metabolic cargo of EVs isolated from bronchoalveolar lavage fluid (BALF), using liquid chromatography-mass spectrometry (LC-MS)-based metabolomic analysis, in patients with sarcoidosis (n=37), compared to healthy controls (n=10). Additionally, the sarcoidosis signature was compared to another pulmonary disorder, anti-synthetase syndrome (ASyS, n=10). Arachidonic acid (AA) results were verified by ELISA. A total of 1202 metabolites were detected, with 111 annotated ones further analyzed. EVs from sarcoidosis patients showed distinct metabolomic profiles compared to both ASyS patients and healthy controls, with 38 annotated metabolites differentially expressed in any of the groups. In both annotated and non-annotated data, sarcoidosis patients clustered separately from ASyS patients and healthy individuals. Furthermore, sarcoidosis patients clustered in 3 subgroups, whereof one was similar to ASyS patients and one stood out as showing higher cell counts in BALF. Higher AA levels were found in sarcoidosis patient EVs by LC-MS, and AA results were verified by ELISA. Our data show that BALF EV metabolites are disease-dependent and support the notion thatsarcoidosis patients should be further subgrouped for better diagnosis and treatment.

immunology↗

bioRxiv2026

Deep brain stimulation reduces subthalamic nucleus pathological dynamics and rescues gait deficits associated with dopamine loss

The Subthalamic Nucleus (STN) regulates movement and is an important clinical target for deep brain stimulation (DBS) in Parkinsons Disease (PD). However, it remains unclear how dopamine loss and DBS influence STN gait encoding. We performed simultaneous recordings from multiple neurons and intermittent DBS in the STN of healthy and dopamine depleted PD mice during voluntary locomotion. We found that dopamine loss resulted in gait deficits manifested as altered stride length of both hindlimbs and forelimbs, which were rescued by intermittent DBS. Furthermore, dopamine loss exaggerated movement encoding of STN population dynamics, and elevates individual STN spiking during movement and beta-rhythmic firing at rest. Despite an overall increase in the fraction of neuron activated by movement, individual neurons gait encoding properties remain similar between healthy and PD mice. While DBS suppressed firing in both healthy and PD mice, it selectively reduced STN beta-rhythmic spiking, desynchronized STN networks, and rescued gait deficits associated with the loss of dopamine. These results suggest that pathological activation and beta synchronization of the STN contributes to motor deficits related to PD, and DBS-induced reduction of beta rhythmic spiking and STN network desynchronization contribute to the therapeutic effects of DBS in PD.

neuroscience↗

bioRxiv2025

Primary CD34+ cells of patients with VEXAS syndrome are highly sensitive to targeted treatment with TAK-243 and pevonedistat

Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic (VEXAS) syndrome is an autoinflammatory disease characterized by somatically acquired UBA1 mutations in hematopoietic stem cells. VEXAS patients present with significant therapeutic challenges such as severe treatment-resistant inflammation and predisposition to myeloid malignancies. In this study, we evaluated the efficacy of TAK-243, a UBA1 inhibitor, and pevonedistat, a NEDD8 inhibitor, in vitro on primary CD34+ hematopoietic stem and progenitor cells (HSPCs) from patients with VEXAS syndrome (n=5), myelodysplastic neoplasms (MDS) (n=10), as well as healthy controls (n=10). Our findings revealed that VEXAS patient-derived HSPCs exhibited significantly higher sensitivity to both TAK-243 (IC50: 22 nM) and pevonedistat (IC50: 553 nM) compared to MDS (IC50: 133 nM and 1048 nM, respectively) and healthy controls (IC50: 192 nM and 1107 nM, respectively) as demonstrated by reduced cell viability. Furthermore, VEXAS CD34+ cells exhibited significantly higher levels of apoptosis after treatment with both inhibitors. These results suggest that TAK-243 and pevonedistat selectively target UBA1-mutated progenitor cells, and indicate a broad therapeutic window in which malignant cells are eradicated but healthy hematopoiesis is not yet compromised. This study provides a strong rationale for further clinical investigation of TAK-243 and pevonedistat as targeted therapies for VEXAS patients, offering hope for improved management of this clinically challenging disorder and contributing to our understanding of its underlying molecular mechanisms.

cancer biology↗

bioRxiv2024

The Condensin II Complex Regulates the Expression of Essential Gene Expression Programs During Erythropoiesis

Erythropoiesis is characterized by dramatic changes in gene expression in the context of a cell that is rapidly proliferating while simultaneously condensing its nucleus in anticipation of enucleation. The mechanisms that maintain high level expression of erythroid genes and promote nuclear condensation remain poorly understood. Condensin II is a ring-like complex that promotes mitotic chromatin condensation and has roles in regulating interphase chromatin architecture and gene expression. We interrogated the role of Condensin II in erythropoiesis using an erythroid-specific deletion of the Condensin II subunit, Ncaph2. Ncaph2 loss resulted in severe embryonic anemia with lethality at embryonic day 13.5. Ncaph2 mutant erythroid cells had dysregulated maturation and disrupted cell cycle progression, but surprisingly Ncaph2 was dispensable for nuclear condensation. Genomic studies revealed that Ncaph2 occupied the promoter of key erythroid and cell cycle genes that were downregulated following Ncaph2 loss. Together, our results demonstrate an essential role for Ncaph2 in the gene expression programs that regulate cell cycle progression and erythroid differentiation, and identify a key role for the Condensin II complex in the regulation of a lineage-specific differentiation program. Summary StatementThe Condensin II complex regulates cell cycle progression and erythroid differentiation, but is dispensable for nuclear condensation during terminal erythroid maturation.

genomics↗

bioRxiv2024

Imaging single particle profiler to study nanoscale bioparticles using conventional confocal microscopy

Single particle profiler is a unique methodology to study nanoscale bioparticles such as liposomes, lipid nanoparticles, extracellular vesicles and lipoproteins in single particle and high throughput manner. The original version requires the single photon counting modules for data acquisition. Here, we present imaging-based SPP (iSPP) which can be performed by imaging a spot over time in common imaging mode with photomultiplier tubes. We also provide a user-friendly software with graphical user interface to facilitate the application of this technique. We demonstrate that iSPP can be used to decipher lipid-protein interactions, membrane modifications by drugs and the heterogeneity of extracellular vesicles isolated from cells lines and urine of human donors.

biophysics↗

bioRxiv2019

ChIPSummitDB: A ChIP-seq-based database of human transcription factor binding sites and the topological arrangements of the proteins bound to them

ChIP-Seq reveals genomic regions where proteins, e.g. transcription factors (TFs) interact with DNA. A substantial fraction of these regions, however, do not contain the cognate binding site for the TF of interest. This phenomenon might be explained by protein-protein interactions and co-precipitation of interacting gene regulatory elements. We uniformly processed 3,727 human ChIP-Seq data sets and determined the cistrome of 292 TFs, as well as the distances between the TF binding motif centers and the ChIP-Seq peak summits. ChIPSummitDB enables the analysis of ChIP-Seq data using multiple approaches. The 292 cistromes and corresponding ChIP-Seq peak sets can be browsed in GenomeView. Overlapping SNPs can be inspected in dbSNPView. Most importantly, the MotifView and PairShiftView pages show the average distance between motif centers and overlapping ChIP-Seq peak summits and distance distributions thereof, respectively. In addition to providing a comprehensive human TF binding site collection, the ChIPSummitDB database and web interface allows for the examination of the topological arrangement of TF complexes genome-wide. ChIPSummitDB is freely accessible at http://summit.med.unideb.hu/summitdb/. The database will be regularly updated and extended with the newly available human and mouse ChIP-Seq data sets.

bioinformatics↗