Herbertduggan0998

Acute ethanol exposure also resulted in the formation of Rad52 foci at levels comparable to Rad52 foci formation after exposure to the DNA alkylating agent methyl methanesulfonate (MMS). MMS exposure is known to induce the intra-S-phase DNA damage checkpoint via Rad53 phosphorylation, but ethanol exposure did not induce Rad53 phosphorylation. Ethanol abrogated the effect of MMS on Rad53 phosphorylation when added simultaneously. From these studies, we propose that acute ethanol exposure induces a change in chromatin leading to sumoylation of specific chromatin structural proteins.Red blood cell (RBC) hitchhiking is a method of drug delivery that can increase drug concentration in target organs by orders of magnitude. In RBC hitchhiking, drug-loaded nanoparticles (NPs) are adsorbed onto red blood cells and then injected intravascularly, which causes the NPs to transfer to cells of the capillaries in the downstream organ. RBC hitchhiking has been demonstrated in multiple species and multiple organs. For example, RBC-hitchhiking NPs localized at unprecedented levels in the brain when using intra-arterial catheters, such as those in place immediately after mechanical thrombectomy for acute ischemic stroke. RBC hitchhiking has been successfully employed in numerous preclinical models of disease, ranging from pulmonary embolism to cancer metastasis. In addition to summarizing the versatility of RBC hitchhiking, we also describe studies into the surprisingly complex mechanisms of RBC hitchhiking as well as outline future studies to further improve RBC hitchhiking's clinical utility. Expected final online publication date for the Annual Review of Biomedical Engineering, Volume 23 is June 2021. Please see http//www.annualreviews.org/page/journal/pubdates for revised estimates.Circadian rhythms describe physiological systems that repeat themselves with a cycle of approximately 24 h. Our understanding of the cellular and molecular origins of these oscillations has improved dramatically, allowing us to appreciate the significant role these oscillations play in maintaining physiological homeostasis. Circadian rhythms allow living organisms to predict and efficiently respond to a dynamically changing environment, set by repetitive day/night cycles. Since circadian rhythms underlie almost every aspect of human physiology, it is unsurprising that they also influence the response of a living organism to disease, stress, and therapeutics. Therefore, not only do the mechanisms that maintain health and disrupt homeostasis depend on our internal circadian clock, but also the way drugs are perceived and function depends on these physiological rhythms. We present a holistic view of the therapeutic process, discussing components such as disease state, pharmacokinetics, and pharmacodynamics, as well as adverse reactions that are critically affected by circadian rhythms. We outline challenges and opportunities in moving toward personalized medicine approaches that explore and capitalize on circadian rhythms for the benefit of the patient. Expected final online publication date for the Annual Review of Biomedical Engineering, Volume 23 is June 2021. Please see http//www.annualreviews.org/page/journal/pubdates for revised estimates.A nature-inspired solution (NIS) methodology is proposed as a systematic platform for innovation and to inform transformative technology required to address Grand Challenges, including sustainable development. Scalability, efficiency, and resilience are essential to nature, as they are to engineering processes. They are achieved through underpinning fundamental mechanisms, which are grouped as recurring themes in the NIS approach hierarchical transport networks, force balancing, dynamic self-organization, and ecosystem properties. To leverage these universal mechanisms, and incorporate them effectively into engineering design, adaptations may be needed to accommodate the different contexts of nature and engineering applications. Nature-inspired chemical engineering takes advantage of the NIS methodology for process intensification, as demonstrated here in fluidization, catalysis, fuel cell engineering, and membrane separations, where much higher performance is achieved by rigorously employing concepts optimized in nature. The same approach lends itself to other applications, from biomedical engineering to information technology and architecture.Over the past three decades, as mechanobiology has become a distinct area of study, researchers have developed novel imaging tools to discover the pathways of biomechanical signaling. Early work with substrate engineering and particle tracking demonstrated the importance of cell-extracellular matrix interactions on the cell cycle as well as the mechanical flux of the intracellular environment. Most recently, tension sensor approaches allowed directly measuring tension in cell-cell and cell-substrate interactions. We retrospectively analyze how these various optical techniques progressed the field and suggest our vision forward for a unified theory of cell mechanics, mapping cellular mechanosensing, and novel biomedical applications for mechanobiology.Rab family GTPases are key organizers of membrane trafficking and function as markers of organelle identity. Accordingly, Rab GTPases often occupy specific membrane domains, and mechanisms exist to prevent the inappropriate mixing of distinct Rab domains. The yeast Golgi complex can be divided into two broad Rab domains Ypt1 (Rab1) and Ypt6 (Rab6) are present at the early/medial Golgi and sharply transition to Ypt31/32 (Rab11) at the late Golgi/trans-Golgi network (TGN). This Rab conversion has been attributed to GTPase-activating protein (GAP) cascades in which Ypt31/32 recruits the Rab-GAPs Gyp1 and Gyp6 to inactivate Ypt1 and Ypt6, respectively. Here we report that Rab transition at the TGN involves additional layers of regulation. We provide new evidence confirming the TRAPPII complex as an important regulator of Ypt6 inactivation and uncover an unexpected role of the Arf1 GTPase in recruiting Gyp1 to drive Ypt1 inactivation at the TGN. CB-5083 ATPase inhibitor Given its established role in directly recruiting TRAPPII to the TGN, Arf1 is therefore a master regulator of Rab conversion on maturing Golgi compartments.