Structural dynamics of nucleic acid and protein is an important physical basis of their functions. These motions are often very difficult to synchronize and too fast to be clearly resolved with the currently available single molecule methods. Here we demonstrate a novel hybrid single molecule approach combining stochastic data analysis with fluorescence correlation that enables investigations of sub-ms unsynchronized structural dynamics of macromolecules. Based on the method, we report the first direct evidence of spontaneous DNA motions at the nucleosome termini. The nucleosome, comprising DNA and a histone core, is the fundamental packing unit of eukaryotic genes that must be accessed during various genome transactions. Spontaneous DNA opening at the nucleosome termini has long been hypothesized to enable gene access in the nucleosome, but has yet to be directly observed. Our approach reveals that DNA termini in the nucleosome open and close repeatedly at 0.1-1 ms(-1). The kinetics depends on salt concentration and DNA-histone interactions but not much on DNA sequence, suggesting that this dynamics is universal and imposes the kinetic limit to gene access. These results clearly demonstrate that our method provides an efficient and robust means to investigate unsynchronized structural changes of DNA at a sub-ms time resolution.
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http://dx.doi.org/10.1093/nar/gkv549 | DOI Listing |
Nat Commun
January 2025
Department of Physics, Harvard University, Cambridge, MA, USA.
High-resolution fluorescence imaging of ultracold atoms and molecules is paramount to performing quantum simulation and computation in optical lattices and tweezers. Imaging durations in these experiments typically range from a millisecond to a second, significantly limiting the cycle time. In this work, we present fast, 2.
View Article and Find Full Text PDFCell Chem Biol
January 2025
Yusuf Hamied Department of Chemistry, University of Cambridge Cambridge CB2 1EW, UK; UK Dementia Research Institute at University of Cambridge Cambridge CB2 0XY, UK. Electronic address:
Synaptic dysfunction is a primary hallmark of both Alzheimer's and Parkinson's disease, leading to cognitive and behavioral decline. While alpha-synuclein, beta-amyloid, and tau are involved in the physiological functioning of synapses, their pathological aggregation has been linked to synaptopathology. The methodology for studying the small-soluble protein aggregates formed by these proteins is limited.
View Article and Find Full Text PDFSci China Life Sci
January 2025
Institute for Regenerative Medicine, State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.
Hair cells in the mammalian cochlea are highly vulnerable to damage from drug toxicity, noise exposure, aging, and genetic mutations, with no capacity for regeneration. Progress in hair cell protection research has been limited by the scarcity of cochlear tissue and suitable in vitro models. Here, we present a novel one-step, self-organizing inner ear organoid system optimized with small molecules, which bypasses the need for multi-step expansion and forced differentiation protocols.
View Article and Find Full Text PDFDiscov Oncol
January 2025
Second Department of Oncology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
Introduction: We conducted a panoramic analysis of GBN5 expression and prognosis in 33 cancers, aiming to deepen the systematic understanding of GBN5 in cancer.
Materials And Methods: We employed a multi-omics approach, including transcriptomic, genomic, proteomic, single-cell cytomic, spatial transcriptomic, and genomic data, to explore the prognostic value and potential oncogenic mechanisms of GBN5 across pan-cancers from multiple perspectives.
Results: We found that GBN5 was differentially expressed in multiple tumors and showed early diagnostic value.
Inflamm Res
January 2025
Departamento de Biomedicina - Unidade de Farmacologia e Terapêutica, Faculdade de Medicina da Universidade do Porto (FMUP), Rua Dr. Plácido da Costa, S/N, Edifício Poente, Piso 3, 4200-450, Porto, Portugal.
Background And Aims: Endocan has been scarcely explored in COVID-19, especially regarding its modulation by veno-venous extracorporeal membrane oxygenation (VV-ECMO), hypertension or previous renin-angiotensin-aldosterone system (RAAS) inhibitors treatment. We compared endocan and other endotheliitis markers in hospitalized COVID-19 patients and assessed their modulation by VV-ECMO, hypertension and previous RAAS inhibitors treatment.
Material And Methods: Serum endocan, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin were measured in "severe" (n = 27), "critically ill" (n = 17) and "critically ill on VV-ECMO" (n = 17) COVID-19 patients at admission, days 3-4, 5-8 and weekly thereafter, and in controls (n = 23) at a single time point.
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