Biology subjects

Brunner, K.

Publications and source records attributed to Brunner, K..

3 recordsLinked to original sources

bioRxiv2023

Moderate Endurance Exercise Increases Arrhythmia Susceptibility and modulates Cardiac Structure and Function in a Sexually Dimorphic manner.

BackgroundWhile moderate endurance exercise has been reported to improve cardiovascular health, its effects on cardiac structure and function are not fully characterized, especially with respect to sexual dimorphism. We aimed to assess the effects of moderate endurance exercise on cardiac physiology in male versus female mice. MethodsC57BL/6J mice of both sexes were run on a treadmill for six weeks. ECG and echocardiography were performed every two weeks. After six weeks of exercise, mice were euthanized, and triple parametric optical mapping was performed on Langendorff perfused hearts to assess cardiac electrophysiology. Arrhythmia inducibility was tested by programmed electrical stimulation. Left ventricular (LV) tissue was fixed, and RNA sequencing was performed to determine exercise-induced transcriptional changes. ResultsExercise-induced LV dilatation was observed in female mice alone, as evidenced by increased LV diameter and reduced LV wall thickness. Increased cardiac output was also observed in female exercised mice but not males. Optical mapping revealed further sexual dimorphism in exercise-induced modulation of cardiac electrophysiology. In female mice, exercise prolonged action potential duration and reduced voltage-calcium influx delay. In male mice, exercise reduced the calcium decay constant, suggesting faster calcium reuptake. Exercise increased arrhythmia inducibility in both male and female mice, however, arrhythmia duration was increased only in females. Lastly, exercise-induced transcriptional changes were sex-dependent: females and males exhibited the most significant changes in contractile versus metabolism-related genes, respectively. ConclusionsOur data suggest that moderate endurance exercise can significantly alter multiple aspects of cardiac physiology in a sex-dependent manner. While some of these effects are beneficial, like improved cardiac mechanical function, others are potentially pro-arrhythmic.

physiology↗

bioRxiv2020

Single-molecule measurements reveal that PARP1 condenses DNA by loop formation

Poly(ADP-ribose) polymerase 1 (PARP1) is an abundant nuclear enzyme that plays important roles in DNA repair, chromatin organization and transcription regulation. Although binding and activation of PARP1 by DNA damage sites has been extensively studied, little is known about how PARP1 binds to long stretches of undamaged DNA and how it could shape chromatin architecture. Here, using a combination of single-molecule techniques including magnetic tweezers and atomic force microscopy, we show that PARP1 binds and condenses undamaged, kilobase-length DNA subject to sub-picoNewton mechanical forces. Decondensation by high force proceeds through a series of discrete increases in extension, indicating that PARP1 stabilizes loops of DNA. This model is supported by DNA braiding experiments which show that PARP1 can bind at the intersection of two separate DNA molecules. PARP inhibitors do not affect the level of condensation of undamaged DNA, but act to block condensation reversal for damaged DNA in the presence of NAD+. Our findings establish a mechanism for PARP1 in the organization of chromatin structure.

biophysics↗

bioRxiv2019

Impact of Ferumoxytol Magnetic Resonance Imaging on the Rhesus Macaque Maternal-Fetal Interface

Ferumoxytol is a superparamagnetic iron oxide nanoparticle (SPION) used off-label as an intravascular magnetic resonance imaging (MRI) contrast agent. Additionally, ferumoxytol-uptake by macrophages facilitates detection of inflammatory sites by MRI through ferumoxytol-induced image contrast changes. Therefore, ferumoxytol-enhanced MRI holds great potential for assessing vascular function and inflammatory response, critical to determine placental health in pregnancy. This study sought to assess the fetoplacental unit and selected maternal tissues, pregnancy outcomes, and fetal well-being after ferumoxytol administration. In initial developmental studies, pregnant rhesus macaques were imaged with and without ferumoxytol administration. Pregnancies went to term with vaginal delivery and infants showed normal growth rates compared to control animals born the same year that did not undergo MRI. To determine the impact of ferumoxytol on the maternal-fetal interface, fetal well-being, and pregnancy outcome, four pregnant rhesus macaques at [~]100 gd (gestational day) underwent MRI before and after ferumoxytol administration. Collection of the fetoplacental unit and selected maternal tissues was performed 3-4 days following ferumoxytol administration. A control group that did not receive ferumoxytol or MRI was used for comparison. Iron levels in fetal and maternal-fetal interface tissues did not vary between groups. There was no significant difference in tissue histopathology with or without exposure to ferumoxytol, and no effect on placental hormone secretion. Together, these results suggest that the use of ferumoxytol and MRI in pregnant rhesus macaques will not introduce a detectable risk to the mother or fetus at the time of imaging or up to one year following normal vaginal delivery.\n\nSummary SentenceFerumoxytol magnetic resonance imaging for non-invasive pregnancy monitoring of the rhesus macaque does not impact histopathology or iron content of the maternal-fetal interface.

physiology↗