The Ludwig Boltzmann Gesellschaft (LBG) is an Austrian network of specialized research institutes that are not part of a university. It was founded in 1961 and named after physicist Ludwig Boltzmann. In 1999, the Ludwig Boltzmann Gesellschaft comprised 131 institutes in the fields of medicine, humanities and social sciences. After 2006, the number of institutes was greatly reduced..
Most breast cancers arise from luminal epithelial cells and 25–30% of these tumours overexpress the ErbB-2 receptor. Herein, a non-transformed, immortalized cell system was used to investigate the effects of ErbB-2 overexpression in luminal epithelial cells. The phenotypic consequence of ErbB-2 overexpression is a shortening of the G1 phase of the cell cycle and early S phase entry, which leads to hyperproliferation. We show that this effect was mediated through the up-regulation of cdk6 and cyclins D1 and E, and enhanced degradation and relocalization of p27Kip1. These changes were effected predominantly through enhanced MAPK signalling, resulting in cdk2 hyperactivation. PI3K signalling also participated in cell cycle progression, since PI3K and MAPK coordinately regulated changes in cyclin D1 and cdk6 expression. Cdk4 activity was not required for cell cycle progression in these cells, and was constitutively inhibited through its association with p16INK4A. MAPK-dependent induction of p21Cip1 was also necessary for G1 phase progression, although its degradation by the proteasome was required for S phase entry. These data provide new insights into the complex molecular mechanisms underlying mitogenic cell cycle control in luminal epithelial cells, the cell type relevant to primary breast cancer, and show how ErbB-2 overexpression subverts this normal control.
The role of YAP (Yes-associated protein 1) and MRTF-A (myocardin-related transcription factor A), two transcriptional co-activators regulated downstream of GPCRs (G protein-coupled receptors) and RhoA, in the growth of glioblastoma cells and in vivo glioblastoma multiforme (GBM) tumor development was explored using human glioblastoma cell lines and tumor-initiating cells derived from patient-derived xenografts (PDX). Knockdown of these co-activators in GSC-23 PDX cells using short hairpin RNA significantly attenuated in vitro self-renewal capability assessed by limiting dilution, oncogene expression, and neurosphere formation. Orthotopic xenografts of the MRTF-A and YAP knockdown PDX cells formed significantly smaller tumors and were of lower morbidity than wild-type cells. In vitro studies used PDX and 1321N1 glioblastoma cells to examine functional responses to sphingosine 1-phosphate (S1P), a GPCR agonist that activates RhoA signaling, demonstrated that YAP signaling was required for cell migration and invasion, whereas MRTF-A was required for cell adhesion; both YAP and MRTF-A were required for proliferation. Gene expression analysis by RNA-sequencing of S1P-treated MRTF-A or YAP knockout cells identified 44 genes that were induced through RhoA and highly dependent on YAP, MRTF-A, or both. Knockdown of F3 (tissue factor (TF)), a target gene regulated selectively through YAP, blocked cell invasion and migration, whereas knockdown of HBEGF (heparin-binding epidermal growth factor-like growth factor), a gene selectively induced through MRTF-A, prevented cell adhesion in response to S1P. Proliferation was sensitive to knockdown of target genes regulated through either or both YAP and MRTF-A. Expression of TF and HBEGF was also selectively decreased in tumors from PDX cells lacking YAP or MRTF-A, indicating that these transcriptional pathways are regulated in preclinical GBM models and suggesting that their activation through GPCRs and RhoA contributes to growth and maintenance of human GBM.
Abstract Respiratory virus surveillance is often constrained by symptomatic testing and centralized sampling, producing blind spots in populations at risk. We developed a transdisciplinary community science framework in which students and teachers co-designed and implemented decentralized respiratory surveillance integrating environmental, molecular, and social data in schools. Within this participatory setting, indoor air COLJ concentrations were monitored alongside student-collected air filter and surface samples, analyzed by digital PCR and sequencing. Community-generated samples reliably captured circulating viruses, while COLJ measurements revealed associations between indoor air quality and pathogen abundance. Quantitative surveys identified social and structural barriers to preventive measures, and shared ownership of study design fostered sustained engagement. By embedding epidemiology within a co-developed, community-driven research process, this study demonstrates how scalable surveillance can close critical data gaps. Our work provides a blueprint for decentralized, community-engaged infectious disease monitoring that positions local partners as active contributors to public health intelligence.
Background: On 1 January 2022, assisted suicide became legal in Austria with the enactment of the Dying Decree Law (Sterbeverfügungsgesetz, StVfG). This law has posed complex practical and ethical challenges for nursing facilities and hospitals. Medical and nursing directors are tasked with guiding their staff amidst legal uncertainties, emotional burdens, and limited institutional dialogue. Objectives: This study aimed to assess directors’ self-reported knowledge of the law, their experiences managing assisted suicide requests, their perceived adequacy of support in navigating the legal framework, and the presence of institutional guidelines. Design: A cross-sectional mixed-methods study. Methods: An online questionnaire was used to collect data from 239 medical and nursing directors across all nine federal states of Austria (mean age = 49.5 years, SD = 8.5; 65.7% female, 32.2% male; 23.7% working in faith-based institutions, 61.9% in non-faith-based institutions, and 14.4% prefer not to disclose). Quantitative data were analysed using chi-square tests, t tests, and ANOVAs, while thematic analysis was applied to open-ended responses. Results: 44.0% of directors knew the regulations of the Dying Decree Law but were insecure in regards to the application in practice, while 13.4% of directors reported no familiarity with Law at all. Legal familiarity correlated with gender ( p = 0.020, V = 0.183) and institutional religious affiliation ( p = 0.019, V = 0.197). Satisfaction with institutional guidelines was linked to gender ( p = 0.004, r = 0.15), religious affiliation ( p = 0.003, r = −0.15), and institution type ( p = 0.011, η² = 0.126). While 36.2% reported no institutional guidelines on assisted suicide, 13.8% were unaware of their existence. Conclusion: The findings reveal knowledge gaps, institutional disparities, and limited guidance on the Dying Decree Law. Directors report insufficient preparedness, highlighting the need for clearer institutional guidelines and enhanced legal, ethical, and psychological support. Trial registration: This study was registered in the Open Science Framework (OSF) at https://osf.io/bgpsa .
Duchenne muscular dystrophy (DMD) is a severe X-linked disorder with progressive myofiber degeneration and fibrosis from dystrophin deficiency. Current therapies are largely supportive with limited anti-fibrotic benefit, prompting new strategies. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) show emerging anti-fibrotic and anti-inflammatory effects. Open-access proteomic and transcriptomic data sets were integrated for in silico analyses, including differential gene expression, weighted gene co-expression network analysis, and pathway enrichment, to identify dysregulated pathways potentially reversible by SGLT2i. Immune cell composition was estimated using CIBERSORTx in human and murine data sets. Therapeutic effects were tested with empagliflozin (EMPA) in mdx mice (30 mg/kg per day for 4 weeks, starting at 12 weeks) and DMDmdx rats (10 mg/kg per day for 4 months, starting at 5 months), with vehicle controls. Validation used quantitative RT-PCR, grip-strength testing, and histologic fibrosis staining. Analyses highlighted dysregulated extracellular matrix organization, cytokine signaling, and immune responses. Forty overlapping genes were identified; hub genes included COL3A1, COL5A2, and TGFB1. EMPA reduced Tgfb1 expression in DMD rats and significantly decreased collagen deposition in skeletal muscle. Functional testing showed longer grip duration in EMPA-treated mice. Immune profiling revealed shifts in T cells and macrophages, indicating immunomodulation. Findings were consistent across species and data modalities analyzed. These results demonstrate that EMPA modulates fibrosis, inflammation, and muscle endurance in DMD models. These data support repurposing SGLT2i as a promising therapeutic strategy for DMD.
