Membrane-associated estrogen receptor “G protein-coupled receptor 30” (GPR30) has been implicated in spatial recognition memory and protection against neuronal death. The present study investigated ...the role of GPR30 in object recognition memory in an Alzheimer's disease (AD) mouse model (5XFAD) by using novel object recognition (NOR) test. Impairment of long-term (24 h) recognition memory was observed in both male and female 5XFAD mice. Selective GPR30 agonist, G-1, ameliorated this impairment in female 5XFAD mice, but not in male mice. Our study demonstrated the ameliorative role of GPR30 in NOR memory impaired by AD pathology in female mice.
The Pleiotropic Drug Resistance (PDR) network is central to the drug response in fungi, and its overactivation is associated with drug resistance. However, gene regulation of the PDR network is not ...well understood. Here, we show that the histone chaperone Rtt106 and the chromatin remodeller SWI/SNF control expression of the PDR network genes and confer drug resistance. In Saccharomyces cerevisiae, Rtt106 specifically localises to PDR network gene promoters dependent on transcription factor Pdr3, but not Pdr1, and is essential for Pdr3-mediated basal expression of the PDR network genes, while SWI/SNF is essential for both basal and drug-induced expression. Also in the pathogenic fungus Candida glabrata, Rtt106 and SWI/SNF regulate drug-induced PDR gene expression. Consistently, loss of Rtt106 or SWI/SNF sensitises drug-resistant S. cerevisiae mutants and C. glabrata to antifungal drugs. Since they cooperatively drive PDR network gene expression, Rtt106 and SWI/SNF represent potential therapeutic targets to combat antifungal resistance.
The ring-shaped complex PCNA coordinates DNA replication, encircling DNA to act as a polymerase clamp and a sliding platform to recruit other replication proteins. PCNA is loaded onto DNA by ...replication factor C, but it has been unknown how PCNA is removed from DNA when Okazaki fragments are completed or the replication fork terminates. Here we show that the Elg1 replication factor C-like complex (Elg1-RLC) functions in PCNA unloading. Using an improved degron system we show that without Elg1, PCNA accumulates on Saccharomyces cerevisiae chromatin during replication. The accumulated PCNA can be removed from chromatin in vivo by switching on Elg1 expression. We find moreover that treating chromatin with purified Elg1-RLC causes PCNA unloading in vitro. Our results demonstrate that Elg1-RLC functions in unloading of both unmodified and SUMOylated PCNA during DNA replication, while the genome instability of an elg1Δ mutant suggests timely PCNA unloading is critical for chromosome maintenance.
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► PCNA accumulates on chromatin in cells lacking Elg1 ► Expressing Elg1 causes PCNA removal from chromatin in vivo ► Treating chromatin with purified Elg1 complex causes PCNA unloading in vitro ► Elg1 complex functions in unloading of both unmodified and SUMOylated PCNA
The sliding clamp PCNA is a crucial component of the DNA replication machinery. Timely PCNA loading and unloading are central for genome integrity and must be strictly coordinated with other DNA ...processing steps during replication. Here, we show that the S. cerevisiae Elg1 replication factor C-like complex (Elg1-RLC) unloads PCNA genome-wide following Okazaki fragment ligation. In the absence of Elg1, PCNA is retained on chromosomes in the wake of replication forks, rather than at specific sites. Degradation of the Okazaki fragment ligase Cdc9 leads to PCNA accumulation on chromatin, similar to the accumulation caused by lack of Elg1. We demonstrate that Okazaki fragment ligation is the critical prerequisite for PCNA unloading, since Chlorella virus DNA ligase can substitute for Cdc9 in yeast and simultaneously promotes PCNA unloading. Our results suggest that Elg1-RLC acts as a general PCNA unloader and is dependent upon DNA ligation during chromosome replication.
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•PCNA is retained behind all replication forks that lack Elg1•Elg1-RLC cannot unload PCNA from unligated lagging-strand DNA•An exogenous ligase can join Okazaki fragments to promote PCNA unloading•Elg1-RLC acts as a general PCNA unloader, dependent upon Okazaki fragment ligation
The sliding clamp PCNA is crucial to DNA replication fidelity, and loading and unloading of PCNA must be strictly regulated. Kubota et al. find that the Elg1 complex unloads PCNA behind all replication forks and is dependent upon successful DNA ligation of Okazaki fragments on the lagging strand.
Initiation of eukaryotic DNA replication requires phosphorylation of the MCM complex by Dbf4-dependent kinase (DDK), composed of Cdc7 kinase and its activator, Dbf4. We report here that budding yeast ...Rif1 (Rap1-interacting factor 1) controls DNA replication genome-wide and describe how Rif1 opposes DDK function by directing Protein Phosphatase 1 (PP1)-mediated dephosphorylation of the MCM complex. Deleting RIF1 partially compensates for the limited DDK activity in a cdc7-1 mutant strain by allowing increased, premature phosphorylation of Mcm4. PP1 interaction motifs within the Rif1 N-terminal domain are critical for its repressive effect on replication. We confirm that Rif1 interacts with PP1 and that PP1 prevents premature Mcm4 phosphorylation. Remarkably, our results suggest that replication repression by Rif1 is itself also DDK-regulated through phosphorylation near the PP1-interacting motifs. Based on our findings, we propose that Rif1 is a novel PP1 substrate targeting subunit that counteracts DDK-mediated phosphorylation during replication. Fission yeast and mammalian Rif1 proteins have also been implicated in regulating DNA replication. Since PP1 interaction sites are evolutionarily conserved within the Rif1 sequence, it is likely that replication control by Rif1 through PP1 is a conserved mechanism.
Central bank digital currencies require the implementation of eKYC to verify whether a trading customer is eligible online. When an organization issues an ID proof of a customer for eKYC, that proof ...is usually achieved in practice by a hierarchy of issuers. However, the customer wants to disclose only part of the issuer's chain and documents to the trading partner due to privacy concerns. In this research, delegatable anonymous credential (DAC) and zero-knowledge range proof (ZKRP) allow customers to arbitrarily change parts of the delegation chain and message body to range proofs expressed in inequalities. That way, customers can protect the privacy they need with their own control. Zero-knowledge proof is applied to prove the inequality between two time stamps by the time stamp server (signature presentation, public key revocation, or non-revocation) without disclosing the signature content and stamped time. It makes it possible to prove that the registration information of the national ID card is valid or invalid while keeping the user's personal information anonymous. This research aims to contribute to the realization of a sustainable financial system based on self-sovereign identity management with privacy-enhanced PKI.
Multi-material structures have become increasingly prevalent in recent years, particularly in the automotive and optical device industries. Achieving a strong bond between different materials in ...these structures is essential, and surface modification is a key step in achieving this bond. Common surface treatment methods include plasma, flame, blasting, and light treatment, but these high-energy methods can sometimes damage the substrate, which is especially problematic in the case of optical devices. Therefore, there is a need for milder surface treatment methods. To address this issue, researchers have developed a custom-made ultraviolet (UV) surface treatment system with an automatic transporter. They investigated the effects of surface modification on indium tin oxide/glass substrates and found that after ∼5 min of treatment with their system, the water contact angle (which is required for coating processes) was reduced, indicating successful surface modification. This was confirmed by narrow-scan x-ray photoelectron spectroscopy measurements, which showed a decay of the C1s peak. The developed UV treatment method is expected to be a useful surface treatment option for adherends in various multi-material structures, particularly those in the optical device industry where substrate damage must be avoided.
In this paper, a novel terrain traversability prediction method is proposed for new operation environments. When an off-road vehicle is operated on rough terrains or slopes made up of unconsolidated ...materials, it is crucial to accurately predict terrain traversability to ensure efficient operations and avoid critical mobility risks. However, the prediction of traversability in new environments is challenging, especially for possibly risky terrains, because the traverse data available for such terrains is either limited or non-existent. To address this limitation, this study proposes an adaptive terrain traversability prediction method based on multi-source transfer Gaussian process regression. The proposed method utilizes the limited data available on low-risk terrains of the target environment to enhance the prediction accuracy on untraversed, possibly higher-risk terrains by leveraging past traverse experiences on multiple types of terrain surface. The effectiveness of the proposed method is demonstrated in scenarios where vehicle slippage and power consumption are predicted using a dataset of various terrain surfaces and geometries. In addition to predicting terrain traversability as continuous values, the utility of the proposed method is demonstrated in binary risk level classification of yet to be traversed steep terrains from limited data on safer terrains.
Hopping robots, called hoppers, are expected to move on rough terrains, such as disaster areas or planetary environments. The uncertainties of the hopping locomotion in such environments are high, ...making path planning algorithms essential to traverse these uncertain environments. Planetary surface exploration requires to generate a path which minimises the risk of failure and maximises the information around the hopper. This paper newly proposes a hopping path planning algorithm for rough terrains locomotion. The proposed algorithm takes into account the motion uncertainties using Markov decision processes (MDPs), and generates paths corresponding to the terrain conditions, or the mission requirements, or both. The simulation results show the effectiveness of the proposed route planning scheme in three cases as the rough terrain, sandy and hard ground environment, and non-smooth borders.
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