Biology subjects

Wieser, M.

Publications and source records attributed to Wieser, M..

4 recordsLinked to original sources

bioRxiv2026

Accurate ΔTm Prediction Without Protein Structure Inputs for Biomolecular Stability

Predicting protein stability, like changes in melting temperature ({Delta}Tm) caused by mutations, is a critical task in therapeutic protein engineering and drug discovery. This is reflected by a growing solution space, including both AI-based sequence and structure based methods. This paper demonstrates that accurate{Delta} Tm prediction does not require structural input features, but can achieve state-of-the-art results with a careful training design for large sequence-based protein language models. We combine an autoresearch-inspired setup search with controlled ablation studies and show that a well-tuned sequence-only ESM2-650M model [6] outperforms structure-informed methods in our benchmark, achieving the lowest error (MAE/RMSE) and competitive Pearson correlation without pH or structural inputs. We further show that choices such as loss function, pooling strategy, auxiliary supervision, and finetuning regime materially affect performance.

bioinformatics↗

bioRxiv2025

Navigating Neurological Re-emergence in Feline Infectious Peritonitis: Challenges and Insights from GS-441524 and Remdesivir Treatment

Case summaryA six-month-old male British Longhair cat presented with acute neurological signs, ocular changes, massive ascites and laboratory parameters consistent with feline infectious peritonitis (FIP). Systemic and neurological signs fully resolved with initial treatment (GS-441524 [BOVA UK, 15 mg/kg PO q24h, 42 days], levetiracetam [20 mg/kg q8h] and prednisolone [1 mg/kg q24h until Day 21 = D-21]). Lethargy and fever reappeared seventeen days after treatment. Four days later, severe multifocal neurological signs reemerged. High-field MRI revealed multifocal intra-axial and intramedullary lesions in the brainstem and cervical spinal cord, severe meningitis and generalised mild ventriculomegaly. Feline coronavirus (FCoV) RNA was detected in the cerebrospinal fluid by RT-qPCR. Abdominal effusion was absent. Serum alpha-1-acid glycoprotein (AGP) was again elevated. FIP re-emergence was suspected, and antiviral treatment was resumed. After one day of GS-441524 treatment (15 mg/kg PO q24h), severe hypoventilation developed, requiring intubation and mechanical ventilation for 1.5 days. Treatment was switched to remdesivir (Veklury, Gilead, 16.7 mg/kg IV q24h) for four days. Oral GS-441524 was then reintroduced (10 mg/kg q12h) and continued until D-84. Treatment resulted in partial recovery with moderate ataxia and reduced left-sided menace response remaining 181 days after starting the second treatment. Relevance and novel informationThis case illustrates the complexity of diagnosing and treating re-emerging FIP-associated neurological signs. AGP monitoring offers a promising noninvasive approach for early detection of relapse. By adapting short- and long-term antiviral treatment and providing intensive care, excellent long-term outcomes can be obtained for cats with severe relapsing FIP-related neurological signs.

microbiology↗

bioRxiv2024

Immortalization of mesenchymal stromal cells by hTERT does not affect the functional properties of secreted extracellular vesicles

Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) have emerged as promising and safe therapeutic agents, however, donor heterogeneities, limited replicative life span and changes in the cellular phenotype throughout in vitro cultivation remain major hurdles for scalable EV production. For these reasons, this study aims to investigate the use of hTERT immortalized ( telomerized) MSCs as a potential source for efficient, standardized, reliable MSC-EVs production by comparing parental primary to their telomerized MSC counterparts. We observed that hTERT expression does not affect cell morphology or cellular doubling time, while ensuring unlimited, stable in vitro propagation. In addition, telomerized WJ-MSCs maintained the canonical expression profile of surface markers and the tri-lineage differentiation potential of their primary counterparts. In terms of EV characteristics, the immortalization by hTERT expression did not affect size, number, cargo composition or biological activity regarding anti-inflammatory, anti-fibrotic and wound healing properties in vitro. In summary, the use of hTERT to immortalize MSCs leads to the creation of cell lines that continuously produce MSC-EVs without altering any key functionalities of the cells or resulting EVs. This suggests that telomerization of human cells from single donors is a promising strategy for generating cell factories that can produce EVs in standardized conditions and at scale and with standardization.

cell biology↗

bioRxiv2024

Profiling microRNA expression during senescence and aging: mining for a diagnostic tool of senescent-cell burden

In the last decade cellular senescence, a hallmark of aging, has come into focus for pharmacologically targeting aging processes. Senolytics are one of these interventive strategies that have advanced into clinical trials, creating an unmet need for minimally invasive biomarkers of senescent cell load to identify patients at need for senotherapy. We created a landscape of miRNA and mRNA expression in five human cell types induced to senescence in-vitro and provide proof-of-principle evidence that miRNA expression can track senescence burden dynamically in-vivo using transgenic p21high senescent cell clearance in HFD fed mice. Finally, we profiled miRNA expression in seven different tissues, total plasma, and plasma derived EVs of young and 25 months old mice. In a systematic analysis, we identified 22 candidate senomiRs with potential to serve as circulating biomarkers of senescence not only in rodents, but also in upcoming human clinical senolytic trials.

molecular biology↗