RNA promotes liquid-liquid phase separation (LLPS) to build membraneless compartments in cells. How distinct molecular compositions are established and maintained in these liquid compartments is ...unknown. Here, we report that secondary structure allows messenger RNAs (mRNAs) to self-associate and determines whether an mRNA is recruited to or excluded from liquid compartments. The polyQ-protein Whi3 induces conformational changes in RNA structure and generates distinct molecular fluctuations depending on the RNA sequence. These data support a model in which structure-based, RNA-RNA interactions promote assembly of distinct droplets and protein-driven, conformational dynamics of the RNA maintain this identity. Thus, the shape of RNA can promote the formation and coexistence of the diverse array of RNA-rich liquid compartments found in a single cell.
Homeostatic regulation of G-quadruplexes (G4s), four-stranded structures that can form in guanine-rich nucleic acids, requires G4 unwinding helicases. The mechanisms that mediate G4 unwinding remain ...unknown. We report the structure of a bacterial RecQ DNA helicase bound to resolved G4 DNA. Unexpectedly, a guanine base from the unwound G4 is sequestered within a guanine-specific binding pocket. Disruption of the pocket in RecQ blocks G4 unwinding, but not G4 binding or duplex DNA unwinding, indicating its essential role in structure-specific G4 resolution. A novel guanine-flipping and sequestration model that may be applicable to other G4-resolving helicases emerges from these studies.
Double-stranded DNA breaks are common cytotoxic lesions that can be repaired by several well-known repair pathways. One of the most prominent repair strategies is homologous recombination (HR). Over ...the years, HR has been studied primarily through biochemical analysis. However, recent advances in single molecule techniques have enabled researchers to investigate the repair mechanisms at the single protein level, with nanometer resolution and millisecond time scale. The ability to fluorescently label different regions of the protein or protein complex allows real-time monitoring of conformational changes, as well as detailed mechanisms with which the proteins target DNA damage and conduct repair. Here, we review some recent single molecule studies that provide new insights into the molecular mechanisms involved in mismatch and homologous repair of DNA.
It is important to ensure the stable operation of PV systems with their increasingly widespread use.For the complex sampling process of most PV fault diagnosis systems, this paper proposes an ...intelligent detection method of PV cell faults based on the I-V characteristic trend, which takes only the I-V characteristic trend of PV cell as a training sample to achieve high accuracy diagnosis of the three states of normal operation, hot-spot faults and abnormal aging. BP (back propagation) neural network algorithm is used as the training algorithm, and the experimental results show that the average accuracy of the BP neural network with the I-V trend as the training object is 99.3%, which achieves high accuracy fault diagnosis.
The integrity of DNA is critical for sustaining the life of any living organism, as DNA is a reservoir of its genetic information. However, DNA is continuously damaged by either normal metabolic ...pathways or environmental insults such as ultraviolet exposure or chemicals. Double-stranded DNA break is one of the most common types of DNA damage that requires activation of homologous recombination (HR) pathway mediated by Rad51 in eukaryotes (Paques & Haber, 1999; Symington, 2002). Rad51 protein forms a helical nucleoprotein filament on resected DNA to initiate homology search but also can interact with other single-stranded DNA (ssDNA)-binding proteins including Srs2. Srs2, a well-known antirecombinase in HR, is an ATP-dependent 3'-5' DNA helicase in the budding yeast Saccharomyces cerevisiae as well as an ssDNA translocase. It disrupts Rad51 filaments, preventing HR (Krejci et al., 2003; Le Breton et al., 2008; Veaute et al., 2003). In the following text, we provide detailed experimental platforms employed to investigate the activity of Rad51 and Srs2 using single-molecule Forster resonance energy transfer and protein-induced fluorescence enhancement. First, we demonstrate how to detect Rad51 filament formation to address the binding site size binding kinetic of the Rad51, as well as the directionality of the filament formation. Next, we explain how to visualize ATP-dependent translocation and unwinding activities of Srs2 on DNA. Lastly, we demonstrate the filament forming activity by Rad51 which is counteracted by the filament removal activity of Srs2.
With recent advances in machine learning, researchers are now able to solve traditional problems with new solutions. In the area of digital watermarking, deep-learning-based watermarking technique is ...being extensively studied. Most existing approaches adopt a similar encoder-driven scheme which we name END (Encoder-NoiseLayer-Decoder) architecture. In this paper, we revamp the architecture and creatively design a decoder-driven watermarking network dubbed De-END which greatly outperforms the existing END-based methods. The motivation for designing De-END originated from the potential drawback we discovered in END architecture: The encoder may embed redundant features that are not necessary for decoding, limiting the performance of the whole network. We conducted a detailed analysis and found that such limitations are caused by unsatisfactory coupling between the encoder and decoder in END. De-END addresses such drawbacks by adopting a Decoder-Encoder-Noiselayer-Decoder architecture. In De-END, the host image is firstly processed by the decoder to generate a latent feature map instead of being directly fed into the encoder. This latent feature map is concatenated to the original watermark message and then processed by the encoder. This change in design is crucial as it makes the feature of encoder and decoder directly shared thus the encoder and decoder are better coupled. We conducted extensive experiments and the results show that this framework outperforms the existing state-of-the-art (SOTA) END-based deep learning watermarking both in visual quality and robustness. On the premise of the same decoder structure, the visual quality (measured by PSNR) of De-END improves by 1.6dB (45.16dB <inline-formula><tex-math notation="LaTeX">\rightarrow</tex-math></inline-formula> 46.84dB), and extraction accuracy after JPEG compression (QF=50) distortion outperforms more than 4% (<inline-formula><tex-math notation="LaTeX">94.9\%\rightarrow 99.1\%</tex-math></inline-formula>).
Chromatin remodelers catalyze dynamic packaging of the genome by carrying out nucleosome assembly/disassembly, histone exchange, and nucleosome repositioning. Remodeling results in evenly spaced ...nucleosomes, which requires probing both sides of the nucleosome, yet the way remodelers organize sliding activity to achieve this task is not understood. Here, we show that the monomeric Chd1 remodeler shifts DNA back and forth by dynamically alternating between different segments of the nucleosome. During sliding, Chd1 generates unstable remodeling intermediates that spontaneously relax to a pre-remodeled position. We demonstrate that nucleosome sliding is tightly controlled by two regulatory domains: the DNA-binding domain, which interferes with sliding when its range is limited by a truncated linking segment, and the chromodomains, which play a key role in substrate discrimination. We propose that active interplay of the ATPase motor with the regulatory domains may promote dynamic nucleosome structures uniquely suited for histone exchange and chromatin reorganization during transcription.
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•Monomeric Chd1 exhibits dynamic shifting of nucleosomal DNA back and forth•Bidirectional sliding by Chd1 entails unstable remodeling intermediates•Limiting the range of the Chd1 DBD interferes with nucleosome sliding•N-terminal chromodomains of Chd1 guard against sliding hexasomes
Chd1 is an ATP-driven chromatin remodeler that evenly repositions nucleosomes along DNA. Qiu et al. demonstrate that a single Chd1 molecule can dynamically shift nucleosomes back and forth. Such bidirectional activity is tightly controlled by two regulatory domains that guide nucleosome sliding and substrate selection.
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•Cinnamaldehyde-based sulfonated amphiphilic all-polyester prodrug, RCSAP.•RCSAP NPs with ROS-responsive core exhibit dual synergistic antibacterial mechanism.•RCSAP NPs show high ...efficacy against E. coli and S. aureus, including MRSA.•RCSAP NPs show accelerated wound healing, low toxicity.
Excessive antibiotic usage has resulted in antibiotic resistance. This work introduces a novel ROS-responsive, cinnamaldehyde (CA)-based sulfonated all-polyester prodrug (RCSAP) to combat antibiotic resistance. RCSAP is a unique amphiphilic pseudo triblock copolymer comprising of two hydrophilic, heparin-mimicking sulfonated polyester (HSP) blocks and a hydrophobic polymeric block containing ROS-responsive CA thioacetal. RCSAP nanoparticles (NPs) not only achieve self-amplifying degradation and release, but orchestrate a “dual wielding” synergistic antibacterial mechanism. HSP shell competes with bacteria for host cell surface binding, hindering its internalization and infection. Simultaneously, ROS-responsive core liberates CA, boosting bacterial membrane permeability. The minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined. RCSAP NPs display exceptional antibacterial efficacy against both E. coli and S. aureus, as confirmed by survival analysis, colony-forming unit (CFU) quantification, microbial growth curve analysis, and live/dead bacterial viability assays. Importantly, RCSAP NPs effectively eradicated methicillin-resistant Staphylococcus aureus (MRSA). In addition, RCSAP NPs possess the unique ability to bind to S. aureus, aggregate and precipitate it. They competitively hinder S. aureus infection in both ARPE-19 and 293 T cells. Molecular simulation further verified the electrostatic interactions between HSP and the S. aureus SpA protein, which may mediate the binding of RCSAP NPs to S. aureus. In vivo assessments demonstrated that RCSAP NPs significantly accelerates wound healing in S. aureus-infected models, with excellent biocompatibility and minimal systemic toxicity. This work paves the way for all-polyester-based nanomedicines harnessing the power of natural antibacterial and heparin-mimicking agents synergistically for enhanced disinfection and wound healing, curbing drug resistance.
Abstract
In order to improve the accuracy of short-term power load forecasting and fully consider the influence of weather factors on power load, a short-term power load forecasting model based on ...multi-factor analysis and Long-Short Term Memory (LSTM) neural network is proposed. Firstly, the correlation between different weather factors and load is analysed using the Spearman coefficient method to extract the weather features that have a greater impact on power load. Then the original time series data are reconstructed using the sliding window method. Finally, the forecasting model is established by using LSTM. The proposed model is validated by using the power load data from the 2016 Electrician’s Cup modelling competition, and compared with other models. The results show that the average absolute percentage error of the forecasting model proposed in this paper reaches 7.41% and the average absolute value error is 380.67 MW, which is better than the other models mentioned in the paper.
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