Non-Coding RNAs Play Significant Roles in Host-Virus Interactions

Previous Dicer immunoprecipitation (IP) discovered an RNA polyphosphatase PIR-1 interacting with Dicer, may participate in RNAi but the mechanism is unrevealed. Here we demonstrate that C. elegans PIR-1 is involved in the RNAi-mediated silencing of Orsay virus via promoting the biogenesis of 23-mer RNAs and the loading of 23-mer RNAs to RDE-1. We also showed that PIR-1 acts as a de facto RNA phosphatase in vivo to regulate triphosphorylated RNAs (ppp-RNAs). Thus, PIR-1 is a conserved master regulator of ppp-RNAs and plays important roles in silencing viral ppp-RNAs and modifying cellular ppp-RNAs.Next we apply PIR-1 in our small RNA cloning strategy. The high-throughput sequencing has become a standard tool for analyzing RNA and DNA. We have developed a new strategy to clone modified/unmodified small RNA in an all-liquid-based reaction carried out in a single PCR tube with as little as 16 ng total RNA. The 7-hour cloning process only needs ~1-hour labor. Moreover, this method can also clone mRNA, simplifying the need to prepare two cloning systems for small RNA and mRNA.At last, we study the function of non-coding RNA in influenza A virus. It utilizes a special process, cap-snatching, to obtain a host capped small RNA for priming viral mRNA synthesis, generating hybrid capped mRNA for translation. Previous studies have been focusing on cap-snatching at thevii5' end of viral mRNA. Here we report two non-canonical cap-snatching regions: one 300-nt upstream of the 3' end of each mRNA generating capped mRNA/ncRNA, and the other in the 5' region of vRNA and mapped primarily at the 2-nt, likely generating ncRNA. We also demonstrate that the influenza virus snatches virus-derived capped RNA in addition to host capped RNA. These findings expand our understanding of the cap-snatching mechanism and suggest that the influenza A virus may utilize this process to diversify its mRNA/ncRNA

The Almost Sure Asymptotic Stability and Boundedness of Stochastic Functional Differential Equations with Polynomial Growth Condition

Stability and boundedness are two of the most important topics in the study of stochastic functional differential equations (SFDEs). This paper mainly discusses the almost sure asymptotic stability and the boundedness of nonlinear SFDEs satisfying the local Lipschitz condition but not the linear growth condition. Here we assume that the coefficients of SFDEs are polynomial or dominated by polynomial functions. We give sufficient criteria on the almost sure asymptotic stability and the boundedness for this kind of nonlinear SFDEs. Some nontrivial examples are provided to illustrate our results

MetaAgents: Simulating Interactions of Human Behaviors for LLM-based Task-oriented Coordination via Collaborative Generative Agents

Significant advancements have occurred in the application of Large Language Models (LLMs) for various tasks and social simulations. Despite this, their capacities to coordinate within task-oriented social contexts are under-explored. Such capabilities are crucial if LLMs are to effectively mimic human-like social behavior and produce meaningful results. To bridge this gap, we introduce collaborative generative agents, endowing LLM-based Agents with consistent behavior patterns and task-solving abilities. We situate these agents in a simulated job fair environment as a case study to scrutinize their coordination skills. We propose a novel framework that equips collaborative generative agents with human-like reasoning abilities and specialized skills. Our evaluation demonstrates that these agents show promising performance. However, we also uncover limitations that hinder their effectiveness in more complex coordination tasks. Our work provides valuable insights into the role and evolution of LLMs in task-oriented social simulations

Asymptotic stability and boundedness of stochastic functional differential equations with Markovian switching

This paper is concerned with the boundedness, exponential stability and almost sure asymptotic stability of stochastic functional differential equations (SFDEs) with Markovian switching. The key technique used is the method of multiple Lyapunov functions. We use two auxiliary functions to dominate the corresponding different Lyapunov function in different mode while the diffusion operator in different model is controlled by other multiple auxiliary functions. Our conditions on the diffusion operator are weaker than those in the related existing works

Adversarial Attack and Defense on Graph Data: A Survey

Deep neural networks (DNNs) have been widely applied to various applications including image classification, text generation, audio recognition, and graph data analysis. However, recent studies have shown that DNNs are vulnerable to adversarial attacks. Though there are several works studying adversarial attack and defense strategies on domains such as images and natural language processing, it is still difficult to directly transfer the learned knowledge to graph structure data due to its representation challenges. Given the importance of graph analysis, an increasing number of works start to analyze the robustness of machine learning models on graph data. Nevertheless, current studies considering adversarial behaviors on graph data usually focus on specific types of attacks with certain assumptions. In addition, each work proposes its own mathematical formulation which makes the comparison among different methods difficult. Therefore, in this paper, we aim to survey existing adversarial learning strategies on graph data and first provide a unified formulation for adversarial learning on graph data which covers most adversarial learning studies on graph. Moreover, we also compare different attacks and defenses on graph data and discuss their corresponding contributions and limitations. In this work, we systemically organize the considered works based on the features of each topic. This survey not only serves as a reference for the research community, but also brings a clear image researchers outside this research domain. Besides, we also create an online resource and keep updating the relevant papers during the last two years. More details of the comparisons of various studies based on this survey are open-sourced at https://github.com/YingtongDou/graph-adversarial-learning-literature.Comment: In submission to Journal. For more open-source and up-to-date information, please check our Github repository: https://github.com/YingtongDou/graph-adversarial-learning-literatur

Design, purification and assessment of GRP78 binding peptide-linked Subunit A of Subtilase cytotoxic for targeting cancer cells

The sequence of primers for GBP-SubA and optimization of E. coli strain and vector of GBP-SubA expression. (DOC 710 kb

Acetylation modification regulates GRP78 secretion in colon cancer cells

High glucose-regulated protein 78 (GRP78) expression contributes to the acquisition of a wide range of phenotypic cancer hallmarks, and the pleiotropic oncogenic functions of GRP78 may result from its diverse subcellular distribution. Interestingly, GRP78 has been reported to be secreted from solid tumour cells, participating in cell-cell communication in the tumour microenvironment. However, the mechanism underlying this secretion remains elusive. Here, we report that GRP78 is secreted from colon cancer cells via exosomes. Histone deacetylase (HDAC) inhibitors blocked GRP78 release by inducing its aggregation in the ER. Mechanistically, HDAC inhibitor treatment suppressed HDAC6 activity and led to increased GRP78 acetylation; acetylated GRP78 then bound to VPS34, a class III phosphoinositide-3 kinase, consequently preventing the sorting of GRP78 into multivesicular bodies (MVBs). Of note, we found that mimicking GRP78 acetylation by substituting the lysine at residue 633, one of the deacetylated sites of HDAC6, with a glutamine resulted in decreased GRP78 secretion and impaired tumour cell growth in vitro. Our study thus reveals a hitherto-unknown mechanism of GRP78 secretion and may also provide implications for the therapeutic use of HDAC inhibitors