A5021983212- PARP inhibition in cancer therapy
- DNA Repair Mechanisms
- Toxin Mechanisms and Immunotoxins
- Cell death mechanisms and regulation
- Integrated Circuits and Semiconductor Failure Analysis
- Genetics, Aging, and Longevity in Model Organisms
- Telomeres, Telomerase, and Senescence
- Carcinogens and Genotoxicity Assessment
- Electrostatic Discharge in Electronics
- CRISPR and Genetic Engineering
- Epigenetics and DNA Methylation
- Nutritional Studies and Diet
- HIV Research and Treatment
- Pesticide Exposure and Toxicity
- Prion Diseases and Protein Misfolding
- Trace Elements in Health
- DNA and Nucleic Acid Chemistry
- Heavy Metal Exposure and Toxicity
- Effects of Radiation Exposure
- Stress Responses and Cortisol
- Calcium signaling and nucleotide metabolism
- Cancer therapeutics and mechanisms
- Neurological diseases and metabolism
- HIV-related health complications and treatments
- Mitochondrial Function and Pathology
University of Konstanz
2015-2024
University Medical Center Freiburg
2014
Offenburg University of Applied Sciences
2014
Leuphana University of Lüneburg
2014
Center for Environmental Health
2013
Massachusetts Institute of Technology
2013
German Cancer Research Center
1995-2009
DKFZ-ZMBH Alliance
1993-2009
Newcastle University
2000-2008
North Tyneside General Hospital
2000-2002
<h3>Objective:</h3> To establish whether HIV disease is associated with abnormal levels of age-related brain atrophy, by estimating apparent age using neuroimaging and exploring these estimates related to status, age, cognitive performance, HIV-related clinical parameters. <h3>Methods:</h3> A large sample virologically suppressed HIV-positive adults (n = 162, 45–82 years) highly comparable HIV-negative controls 105) were recruited as part the Comorbidity in Relation AIDS (COBRA)...
Poly(ADP-ribosyl)ation is a eukaryotic posttranslational modification of proteins that strongly induced by the presence DNA strand breaks and plays role in repair recovery cells from damage. We compared poly(ADP-ribose) polymerase (PARP; EC 2.4.2.30) activities Percoll gradient-purified, permeabilized mononuclear leukocytes mammalian species different maximal life span. Saturating concentrations double-stranded octameric oligonucleotide were applied to provide direct stimulation PARP. Our...
Activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) is an early response cells exposed to DNA-damaging compounds such as nitric oxide (NO) or reactive oxygen intermediates (ROI). Excessive poly-(ADP-ribose) formation by PARP has been assumed deplete cellular NAD+ pools and induce death several cell types, including loss insulin-producing islet in type I diabetes. In present study we used from mice with a disrupted thus inactivated gene provide direct evidence for causal...
Imbalance between pro- and antioxidant species (e.g. during aging) plays a crucial role for vascular function is associated with oxidative gene regulation modification. Vascular aging progressive deterioration of homeostasis leading to reduced relaxation, hypertrophy, higher risk thrombotic events. These effects can be explained by reduction in free bioavailable nitric oxide that inactivated an age-dependent increase superoxide formation. In the present study, mitochondria as source reactive...
Poly(ADP-ribose) (PAR) is synthesized by poly(ADP-ribose) polymerases in response to genotoxic stress and interacts non-covalently with DNA damage checkpoint repair proteins. Here, we present a variety of techniques analyze this interaction terms selectivity affinity. In vitro PAR was end-labeled using carbonyl-reactive biotin analog. Binding HPLC-fractionated chains the tumor suppressor protein p53 nucleotide excision XPA assessed novel electrophoretic mobility shift assay (EMSA). Long...
Despite successful antiretroviral therapy, people living with HIV (PLWH) may show signs of premature/accentuated aging. We compared established biomarkers aging in PLWH, appropriately chosen HIV-negative individuals, and blood donors, explored factors associated biological age advancement.Cross-sectional analysis 134 PLWH on suppressive 79 lifestyle-comparable controls aged 45 years or older from the Co-morBidity Relation to AIDS (COBRA) cohort, 35 age-matched donors.Biological was estimated...
The post-translational modification poly(ADP-ribosyl)ation (PARylation) plays key roles in genome maintenance and transcription. Both non-covalent poly(ADP-ribose) binding covalent PARylation control protein functions, however, it is unknown how the two modes of crosstalk mechanistically. Employing tumor suppressor p53 as a model substrate, this study provides detailed insights into interplay between unravels its functional significance regulation p53. We reveal that multifunctional...
Abstract Self-rated health (SRH) is one of the most frequently used indicators in and social research. Its robust association with mortality very different populations implies that it a comprehensive measure status may even reflect condition human organism beyond clinical diagnoses. Yet biological basis SRH poorly understood. We data from three independent European population samples (N approx. 15,000) to investigate associations 150 biomolecules blood or urine (biomarkers). Altogether 57...
Abstract Poly-ADP-ribosylation (PARylation) is a fully reversible post-translational modification with key roles in cellular physiology. Due to the multi-domain structure of poly(ADP-ribose) polymerase-1 (PARP1) and highly dynamic nature PARylation reaction, studies on biochemical mechanism structural dynamics remain challenging. Here, we report label-free, time-resolved monitoring PARP1-dependent using ATR-FTIR spectroscopy. This includes PARP1 activation by binding DNA strand break models,...
Minocycline prevents oxidative protein modifications and damage in disease models associated with inflammatory glial activation stress. Although the drug has been assumed to act by preventing up-regulation of proinflammatory enzymes, we probed here its direct chemical interaction reactive oxygen species. The antibiotic did not react superoxide or •NO radicals, but peroxynitrite (PON) was scavenged range ∼1 μm minocycline below. pharmacologically relevant concentrations PON corroborated...