DNA loop extrusion is asymmetric but can switch direction
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Additive manufacturing of a 3D-segmented plastic scintillator detector for tracking and calorimetry of elementary particles
Plastic scintillators, segmented into small, optically isolated voxels, are used for detecting elementary particles and provide reliable particle identification with nanosecond time resolution. Building large detectors requires the production and precise alignment of millions of individual units, a process that is time-consuming, cost-intensive, and difficult to scale. Here, we introduce an additive manufacturing process chain capable of producing plastic-based scintillator detectors as a single, monolithic structure. Unlike previous manufacturing methods, this approach consolidates all production steps within one machine, creating a detector that integrates and precisely aligns its voxels into a unified structure. By combining fused deposition modeling with an injection process optimized for fabricating scintillation geometries, we produced an additively manufactured fine-granularity plastic scintillator detector with performance comparable to the state of the art, and demonstrated its capabilities for 3D tracking of elementary particles and energy-loss measurement. This work presents an efficient and economical production process for manufacturing plastic-based scintillator detectors, adaptable to various sizes and geometries.
Structural basis for intrinsic strand displacement activity of mitochondrial DNA polymerase
Members of the Pol A family of DNA polymerases, found across all domains of life, utilize various strategies for DNA strand separation during replication. In higher eukaryotes, mitochondrial DNA polymerase γ relies on the replicative helicase TWINKLE, whereas the yeast ortholog, Mip1, can unwind DNA independently. Using Mip1 as a model, we present a series of high-resolution cryo-EM structures that capture the process of DNA strand displacement. Our data reveal previously unidentified structural elements that facilitate the unwinding of the downstream DNA duplex. Yeast cells harboring Mip1 variants defective in strand displacement exhibit impaired oxidative phosphorylation and loss of mtDNA, corroborating the structural observations. This study provides a molecular basis for the intrinsic strand displacement activity of Mip1 and illuminates the distinct unwinding mechanisms utilized by Pol A family DNA polymerases.
KorB switching from DNA-sliding clamp to repressor mediates long-range gene silencing in a multi-drug resistance plasmid
Examples of long-range gene regulation in bacteria are rare and generally thought to involve DNA looping. Here, using a combination of biophysical approaches including X-ray crystallography and single-molecule analysis for the KorB–KorA system in Escherichia coli, we show that long-range gene silencing on the plasmid RK2, a source of multi-drug resistance across diverse Gram-negative bacteria, is achieved cooperatively by a DNA-sliding clamp, KorB, and a clamp-locking protein, KorA. We show that KorB is a CTPase clamp that can entrap and slide along DNA to reach distal target promoters up to 1.5 kb away. We resolved the tripartite crystal structure of a KorB–KorA–DNA co-complex, revealing that KorA latches KorB into a closed clamp state. DNA-bound KorA thus stimulates repression by stalling KorB sliding at target promoters to occlude RNA polymerase holoenzymes. Together, our findings explain the mechanistic basis for KorB role switching from a DNA-sliding clamp to a co-repressor and provide an alternative mechanism for long-range regulation of gene expression in bacteria.
Surface-hydroxylated single-atom catalyst with an isolated Co-O-Zn configuration achieves high selectivity in regulating active species
Single-atom catalysts (SACs) are emerging as potent tools for the selective regulation of active species, offering substantial promise for green and sustainable Fenton catalysis. However, current SACs face limitations due to the specificity of their supports, which only allow selective regulation within certain oxidant systems. This constraint makes targeted regulation across different systems challenging. In response, this study designs a SAC, termed CoSAs-ZnO, featuring surface hydroxylation and an isolated asymmetric Co-O-Zn configuration. This SAC can realize a nearly 100% selective generation of sulfate radicals (SO4•−) and singlet oxygen (1O2) in peroxymonosulfate (PMS) and peracetic acid (PAA) systems, respectively. Moreover, the PMS-activated system can efficiently treat electron-deficient-dominated and refractory benzoic acid wastewater, achieving 100.0% removal in multiple consecutive pilot-scale experiments. The PAA-activated system facilitates the rapid conversion of benzyl alcohol to benzaldehyde, with a high selectivity of 89.0%. Detailed DFT calculations reveal that the surface hydroxyl groups on ZnO play a critical role in modulating the adsorption configurations of the oxidants, thus enabling the selective generation of specific active species in each system. This study provides insights into the design of SACs for multifunctional applications and paves the way for their deployment in wastewater treatment and high-value chemical conversion.
Personalized bioceramic grafts for craniomaxillofacial bone regeneration
The reconstruction of craniomaxillofacial bone defects remains clinically challenging. To date, autogenous grafts are considered the gold standard but present critical drawbacks. These shortcomings have driven recent research on craniomaxillofacial bone reconstruction to focus on synthetic grafts with distinct materials and fabrication techniques. Among the various fabrication methods, additive manufacturing (AM) has shown significant clinical potential. AM technologies build three-dimensional (3D) objects with personalized geometry customizable from a computer-aided design. These layer-by-layer 3D biomaterial structures can support bone formation by guiding cell migration/proliferation, osteogenesis, and angiogenesis. Additionally, these structures can be engineered to degrade concomitantly with the new bone tissue formation, making them ideal as synthetic grafts. This review delves into the key advances of bioceramic grafts/scaffolds obtained by 3D printing for personalized craniomaxillofacial bone reconstruction. In this regard, clinically relevant topics such as ceramic-based biomaterials, graft/scaffold characteristics (macro/micro-features), material extrusion-based 3D printing, and the step-by-step workflow to engineer personalized bioceramic grafts are discussed. Importantly, in vitro models are highlighted in conjunction with a thorough examination of the signaling pathways reported when investigating these bioceramics and their effect on cellular response/behavior. Lastly, we summarize the clinical potential and translation opportunities of personalized bioceramics for craniomaxillofacial bone regeneration.
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