A5071576337- Sulfur Compounds in Biology
- Folate and B Vitamins Research
- Heme Oxygenase-1 and Carbon Monoxide
- NF-κB Signaling Pathways
- Redox biology and oxidative stress
- Nitric Oxide and Endothelin Effects
- Metabolism and Genetic Disorders
- Amino Acid Enzymes and Metabolism
- Trace Elements in Health
- Immune Cell Function and Interaction
- Natural product bioactivities and synthesis
- Nutrition and Health in Aging
- Cassava research and cyanide
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- GDF15 and Related Biomarkers
- Bioactive Compounds and Antitumor Agents
- Neonatal Health and Biochemistry
- Metabolomics and Mass Spectrometry Studies
- Macrophage Migration Inhibitory Factor
- SARS-CoV-2 and COVID-19 Research
- Sepsis Diagnosis and Treatment
- PARP inhibition in cancer therapy
- Heavy Metal Exposure and Toxicity
- COVID-19 epidemiological studies
- Mitochondrial Function and Pathology
Medical University of Vienna
2024
Instituto Gulbenkian de Ciência
2016-2022
Austrian Academy of Sciences
2020
CeMM Research Center for Molecular Medicine
2020
University of Lisbon
2013-2018
Superspreading events shaped the coronavirus disease 2019 (COVID-19) pandemic, and their rapid identification containment are essential for control. Here, we provide a national-scale analysis of severe acute respiratory syndrome 2 (SARS-CoV-2) superspreading during first wave infections in Austria, country that played major role initial virus transmissions Europe. Capitalizing on Austria's well-developed epidemiological surveillance system, identified SARS-CoV-2 clusters performed deep...
Abstract Hydrogen sulfide (H 2 S) impairs mitochondrial respiration by potently inhibiting the heme-copper cytochrome c oxidase. Since many prokaryotes, including Escherichia (E.) coli , generate H S and encounter high levels particularly in human gut, herein we tested whether bacteria can sustain sulfide-resistant O -dependent respiration. E. has three respiratory oxidases, cyanide-sensitive bo 3 enzyme two bd oxidases much less sensitive to cyanide. Working on isolated enzymes, found that,...
Several classes of antibiotics have long been known to beneficial effects that cannot be explained strictly on the basis their capacity control infectious agent. Here, we report tetracycline antibiotics, which target mitoribosome, protected against sepsis without affecting pathogen load. Mechanistically, found mitochondrial inhibition protein synthesis perturbed electron transport chain (ETC) decreasing tissue damage in lung and increasing fatty acid oxidation glucocorticoid sensitivity...
Significance Sepsis remains a leading cause of death. New insights into its pathophysiology are likely to be key the development effective therapeutic strategies against sepsis. Given role GDF15 in metabolism regulation and cachexia during late stages cancer, features that also occur sepsis, elucidation possible mechanistic sepsis is great importance. We find septic patients have very high levels peripheral blood, which correlate with clinical outcomes. Using Gdf15 -deficient mice, we show...
Cystathionine beta-synthase (CBS) catalyzes the formation of cystathionine from homocysteine and serine. CBS is allosterically activated by S-adenosylmethionine (SAM), which binds to its C-terminal regulatory domain. Mutations in this domain lead variants with high residual activity but lacking SAM activation. We characterized six (p.P427L, p.D444N, p.V449G, p.S500L, p.K523Sfs*18, p.L540Q). To understand effect mutations on functional/structural properties CBS, we performed dynamic light...
Structural-functional platform unravels new roles for ZinT in cobalt, mercury and cadmium resistance, providing clues into the metal binding mechanism.
The human disease classical homocystinuria results from mutations in the gene encoding pyridoxal 5′‐phosphate‐ (PLP‐) dependent cystathionine β ‐synthase (CBS), a key enzyme transsulfuration pathway that controls homocysteine levels, and is major source of signaling molecule hydrogen sulfide (H 2 S). CBS activity, contributing to cellular redox homeostasis, positively regulated by S ‐adenosyl‐ L ‐methionine (AdoMet) but fully inhibited upon CO or NO• binding noncatalytic heme moiety. Despite...
Abstract Superspreading events shape the COVID-19 pandemic. Here we provide a national-scale analysis of SARS-CoV-2 outbreaks in Austria, country that played major role for virus transmission across Europe and beyond. Capitalizing on national epidemiological surveillance system, performed deep whole-genome sequencing isolates from 576 samples to cover Austrian clusters. Our data chart map early viral spreading Europe, including path low-frequency mutations fixation. Detailed surveys enabled...
Anthracyclines are among the most used and effective anticancer drugs. Their activity has been attributed to DNA double-strand breaks resulting from topoisomerase II poisoning eviction of histones select sites in genome. Here, we show that extensively anthracyclines Doxorubicin, Daunorubicin, Epirubicin decrease transcription nuclear factor kappa B (NF-κB)-dependent gene targets, but not interferon-responsive genes primary mouse (Mus musculus) macrophages. Using an NMR-based structural...
Summary Synergy of resistance and disease tolerance mechanisms is necessary for an effective immune response leading to survival return homeostasis when organism challenged by infection. Antibiotics are used their enhancement capabilities decreasing pathogen load, but several classes have long been known beneficial effects that cannot be explained strictly on the basis capacity control infectious agent. Here we report tetracycline antibiotics, a class ribosome-targeting drugs, robustly...
Abstract Sepsis is a life-threatening organ dysfunction condition caused by dysregulated host response to an infection. Here we report that the circulating levels of growth-differentiation factor-15 (GDF15) are strongly increased in septic shock patients and correlate with mortality. In mice, find peptidoglycan potent ligand signals through TLR2-Myd88 axis for secretion GDF15 Gdf15 -deficient animals protected against abdominal sepsis due chemokine CXC 5 (CXCL5)-mediated recruitment...
Abstract Anthracyclines are among the most used and effective anticancer drugs. Their activity has been attributed to DNA double-strand breaks resulting from topoisomerase II poisoning eviction of histones select sites in genome. Here we show that extensively anthracyclines Doxorubicin, Daunorubicin Epirubicin, decrease transcription nuclear factor kappa B (NF-κB)-dependent gene targets, but not interferon responsive genes. Using an NMR-based structural approach, demonstrate disturb...