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Exposure to environmental contaminants can result in profound effects on the host immune system. One class of environmental toxicants, known as dioxins, are persistent environmental contaminants termed “forever chemicals”. The archetype toxicant from this group of chemicals is 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD), an immunotoxicant that activates the aryl-hydrocarbon receptor pathway leading to a variety of changes in immune cell responses. Immune cell functions are crucial to the development and maintenance of healthy reproduction. Immune cells facilitate tolerance between at the maternal-fetal interface between the parent and the semi-allogenic fetus and help defend the gravid reproductive tract from infectious assault. Epidemiological studies reveal that exposure to environmental contaminants (such as TCDD) are linked to adverse reproductive health outcomes including endometriosis, placental inflammation, and preterm birth. However, little is known about the molecular mechanisms that underpin h 

Abstract Proximity ligation assays (PLAs) use specific antibodies to detect endogenous protein‐protein interactions. PLAs are a highly useful biochemical technique that allow two proteins within proximity to be visualized with fluorescent probes amplified by PCR. While this technique has gained prominence, the use of a PLA in mouse skeletal muscle (SkM) is novel. In this article, we discuss how the PLA method can be used in SkM to study the protein‐protein interactions within mitochondria‐endoplasmic reticulum contact sites (MERCs). © 2025 The Author(s). Current Protocols published by Wiley Periodicals LLC. Basic Protocol: Proximity ligation assay for skeletal muscle tissue and myoblast for MERC proteins 

Tweetable abstract Mitochondrial transplantation has been used to treat various diseases associated with mitochondrial dysfunction. Here, we highlight the considerations in quality control mechanisms that should be considered in the context of mitochondrial transplantation. 

Abstract Machine learning has proven useful in analyzing complex biological data and has greatly influenced the course of research in structural biology and precision medicine. Deep neural network models oftentimes fail to predict the structure of complex proteins and are heavily dependent on experimentally determined structures for their training and validation. Single‐particle cryogenic electron microscopy (cryoEM) is also advancing the understanding of biology and will be needed to complement these models by continuously supplying high‐quality experimentally validated structures for improvements in prediction quality. In this perspective, the significance of structure prediction methods is highlighted, but the authors also ask, what if these programs cannot accurately predict a protein structure important for preventing disease? The role of cryoEM is discussed to help fill the gaps left by artificial intelligence predictive models in resolving targetable proteins and protein complexes that will pave the way for personalized therapeutics. 

Introduction: Many studies in mice have demonstrated that cardiac-specific innate immune signaling pathways can be reprogrammed to modulate inflammation in response to myocardial injury and improve outcomes. While the echocardiography standard parameters of left ventricular (LV) ejection fraction, fractional shortening, end-diastolic diameter, and others are used to assess cardiac function, their dependency on loading conditions somewhat limits their utility in completely reflecting the contractile function and global cardiovascular efficiency of the heart. A true measure of global cardiovascular efficiency should include the interaction between the ventricle and the aorta (ventricular-vascular coupling, VVC) as well as measures of aortic impedance and pulse wave velocity. Methods: We measured cardiac Doppler velocities, blood pressures, along with VVC, aortic impedance, and pulse wave velocity to evaluate global cardiac function in a mouse model of cardiac-restricted low levels of TRAF2 overexpression that conferred cytoprotection in the heart. Results: While previous studies reported that response to myocardial infarction and reperfusion was improved in the TRAF2 overexpressed mice, we found that TRAF2 mice had significantly lower cardiac systolic velocities and accelerations, diastolic atrial velocity, aortic pressures, rate-pressure product, LV contractility and relaxation, and stroke work when compared to littermate control mice. Also, we found significantly longer aortic ejection time, isovolumic contraction and relaxation times, and significantly higher mitral early/atrial ratio, myocardial performance index, and ventricular vascular coupling in the TRAF2 overexpression mice compared to their littermate controls. We found no significant differences in the aortic impedance and pulse wave velocity. Discussion: While the reported tolerance to ischemic insults in TRAF2 overexpression mice may suggest enhanced cardiac reserve, our results indicate diminished cardiac function in these mice.