The dynamic transient formation and depletion of G-quadruplexes regulate gene replication and transcription. This process was found to be related to various diseases such as cancer and premature aging. We report on the engineering of nucleic acid modules revealing dynamic, transient assembly and disassembly of G-quadruplex structures and G-quadruplex-based DNAzymes, gated transient processes, and cascaded dynamic transient reactions that involve G-quadruplex and DNAzyme structures. The dynamic transient processes are driven by functional DNA reaction modules activated by a fuel strand and guided toward dissipative operation by a nicking enzyme (Nt.BbvCI). The dynamic networks were further characterized by computational simulation of the experiments using kinetic models, allowing us to predict the dynamic performance of the networks under different auxiliary conditions applied to the systems. The systems reported herein could provide functional DNA machineries for the spatiotemporal control of G-quadruplex structures perturbing gene expression and thus provide a therapeutic means for related emergent diseases.
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http://dx.doi.org/10.1021/acsnano.1c11631 | DOI Listing |
Elife
January 2025
Eikon Therapeutics Inc, Hayward, United States.
The regulation of cell physiology depends largely upon interactions of functionally distinct proteins and cellular components. These interactions may be transient or long-lived, but often affect protein motion. Measurement of protein dynamics within a cellular environment, particularly while perturbing protein function with small molecules, may enable dissection of key interactions and facilitate drug discovery; however, current approaches are limited by throughput with respect to data acquisition and analysis.
View Article and Find Full Text PDFBackground: An intact blood-brain barrier (BBB) is critical for optimal brain health, and even transient or highly localized disruption of the BBB can have devastating consequences for neural functioning. BBB breakdown has been implicated in Alzheimer's Disease (AD) pathogenesis, and elevated BBB permeability has been observed in APOE e4 carriers compared to non-carriers. As prior studies have focused on a priori, AD-vulnerable regions rather than whole-brain analyses, little is understood about broader patterns of BBB breakdown that may relate to AD risk.
View Article and Find Full Text PDFJ Phys Chem B
January 2025
Dipartimento di Fisica, Università di Trieste, Strada Costiera 11, 34151 Trieste, Italy.
We reassess the modeling of amorphous silica bilayers as a 2D classical system whose particles interact with an effective pairwise potential. We show that it is possible to reparametrize the potential developed by Roy, Heyde, and Heuer to quantitatively match the structural details of the experimental samples. We then study the glassy dynamics of the reparametrized model at low temperatures.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Biomedical Research Networking Center in Bioengineering Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Madrid, Spain.
Background: Recent studies in brain functional connectivity (FC) have shifted focus to dynamic functional connectivity (dFC), exploring transient aspects of FC over time. This shift is particularly relevant for Alzheimer's Disease (AD), as it involves altered cognition-supporting networks. Our study aims to characterize the evolution of dFC across the entire pre-dementia AD spectrum using Amplitude Envelope Correlation (AEC) recurrence matrices and to link this to cognitive decline.
View Article and Find Full Text PDFJ Chem Phys
January 2025
Department of Chemistry and Paula M. Trienens Institute for Sustainability and Energy Northwestern University, Evanston, Illinois 60208-3113, USA.
Organic donor-acceptor (D-A) cocrystals are gaining attention for their potential applications in optoelectronic devices. This study explores the dynamics of charge transfer (CT) and triplet exciton formation in various D-A cocrystals. By examining a series of D-A cocrystals composed of coronene (COR), peri-xanthenoxanthene (PXX), and perylene (PER) donors paired with N,N-bis(3'-pentyl)perylene-3,4:9,10-bis(dicarboximide) (PDI), naphthalene-1,4:5,8-tetracarboxy-dianhydride (NDA), or pyrene-4,5,9,10-tetraone (PTO) acceptors, using transient absorption microscopy and time-resolved electron paramagnetic resonance spectroscopy, we find that the strength of the CT interaction influences the nature and yield of triplet excitons produced by CT state recombination.
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