NudC L279P Mutation Destabilizes Filamin A by Inhibiting the Hsp90 Chaperoning Pathway and Suppresses Cell Migration

Filamin A, the first discovered non-muscle actin filament cross-linking protein, plays a crucial role in regulating cell migration that participates in diverse cellular and developmental processes. However, the regulatory mechanism of filamin A stability remains unclear. Here, we find that nuclear distribution gene C (NudC), a cochaperone of heat shock protein 90 (Hsp90), is required to stabilize filamin A in mammalian cells. Immunoprecipitation-mass spectrometry and western blotting analyses reveal that NudC interacts with filamin A. Overexpression of human NudC-L279P (an evolutionarily conserved mutation in NudC that impairs its chaperone activity) not only decreases the protein level of filamin A but also results in actin disorganization and the suppression of cell migration. Ectopic expression of filamin A is able to reverse these defects induced by the overexpression of NudC-L279P. Furthermore, Hsp90 forms a complex with filamin A. The inhibition of Hsp90 ATPase activity by either geldanamycin or radicicol decreases the protein stability of filamin A. In addition, ectopic expression of Hsp90 efficiently restores NudC-L279P overexpression-induced protein stability and functional defects of filamin A. Taken together, these data suggest NudC L279P mutation destabilizes filamin A by inhibiting the Hsp90 chaperoning pathway and suppresses cell migration

Event-Centric Query Expansion in Web Search

In search engines, query expansion (QE) is a crucial technique to improve search experience. Previous studies often rely on long-term search log mining, which leads to slow updates and is sub-optimal for time-sensitive news searches. In this work, we present Event-Centric Query Expansion (EQE), a novel QE system that addresses these issues by mining the best expansion from a significant amount of potential events rapidly and accurately. This system consists of four stages, i.e., event collection, event reformulation, semantic retrieval and online ranking. Specifically, we first collect and filter news headlines from websites. Then we propose a generation model that incorporates contrastive learning and prompt-tuning techniques to reformulate these headlines to concise candidates. Additionally, we fine-tune a dual-tower semantic model to function as an encoder for event retrieval and explore a two-stage contrastive training approach to enhance the accuracy of event retrieval. Finally, we rank the retrieved events and select the optimal one as QE, which is then used to improve the retrieval of event-related documents. Through offline analysis and online A/B testing, we observe that the EQE system significantly improves many metrics compared to the baseline. The system has been deployed in Tencent QQ Browser Search and served hundreds of millions of users. The dataset and baseline codes are available at https://open-event-hub.github.io/eqe .Comment: ACL 2023 Industry Trac

Title2Event: Benchmarking Open Event Extraction with a Large-scale Chinese Title Dataset

Event extraction (EE) is crucial to downstream tasks such as new aggregation and event knowledge graph construction. Most existing EE datasets manually define fixed event types and design specific schema for each of them, failing to cover diverse events emerging from the online text. Moreover, news titles, an important source of event mentions, have not gained enough attention in current EE research. In this paper, We present Title2Event, a large-scale sentence-level dataset benchmarking Open Event Extraction without restricting event types. Title2Event contains more than 42,000 news titles in 34 topics collected from Chinese web pages. To the best of our knowledge, it is currently the largest manually-annotated Chinese dataset for open event extraction. We further conduct experiments on Title2Event with different models and show that the characteristics of titles make it challenging for event extraction, addressing the significance of advanced study on this problem. The dataset and baseline codes are available at https://open-event-hub.github.io/title2event.Comment: EMNLP 202

PKD1 Phosphorylation-Dependent Degradation of SNAIL by SCF-FBXO11 Regulates Epithelial-Mesenchymal Transition and Metastasis

SummaryMetastatic dissemination is often initiated by the reactivation of an embryonic development program referred to as epithelial-mesenchymal transition (EMT). The transcription factor SNAIL promotes EMT and elicits associated pathological characteristics such as invasion, metastasis, and stemness. To better understand the posttranslational regulation of SNAIL, we performed a luciferase-based, genome-wide E3 ligase siRNA library screen and identified SCF-FBXO11 as an important E3 that targets SNAIL for ubiquitylation and degradation. Furthermore, we discovered that SNAIL degradation by FBXO11 is dependent on Ser-11 phosphorylation of SNAIL by protein kinase D1 (PKD1). FBXO11 blocks SNAIL-induced EMT, tumor initiation, and metastasis in multiple breast cancer models. These findings establish the PKD1-FBXO11-SNAIL axis as a mechanism of posttranslational regulation of EMT and cancer metastasis

All-optical format conversion-based flexible optical interconnection using nonlinear MZI with nested-pump assisted NOLM

An all-optical format conversion (AOFC) scheme of star-m-ary quadrature amplitude modulation (star-mQAM) based on a nonlinear Mach-Zehnder interferometer (MZI) with nested-pump assisted nonlinear optical loop mirror (nested-PA-NOLM) is proposed and numerically simulated. In this scheme, input multi-Gbps star-8QAM signals can be converted into three quadrature phase shift keying (QPSK) signals (namely QPSK-A, -B and -C) through the PA-NOLM under different input power of the signal and the pump. The nonlinear MZI is formed by two PA-NOLMs of the upper and the lower arms, the former and the latter 3-dB optical couplers (OCs), a directional variable optical attenuator (VOA) in the upper arm and a directional variable phase shifter (VPS) in the lower arm. A VOA and a VPS are used to adjust the power ratio (PR) and relative phase shift (RPS) between any two of QPSK-A, -B and -C. When any two adjusted signals in QPSK-A, -B and -C are coherently superposed, the aggregated star-8QAM signal can be extracted again. Furthermore, the proposed scheme can also be used to convert the 20 Gbps bipolar 4-ary pulse amplitude modulation (PAM4) signal into two 10 Gbps BPSK signals and a 20 Gbps QPSK signal. When the proposed scheme is combined with the phase-sensitive amplification (PSA), it can also be used to convert one 16QAM into two QPSK signals. The scheme performance is analyzed via constellation diagrams, power waveforms, the error vector magnitude (EVM) and the bit error rate (BER) of the optical signals. The scheme can not only be deployed in optical gateways to connect optical networks using different modulation formats, but also has a potential applied advantage in security information transmission between different optical networks