A novel role for IGF-1R in p53-mediated apoptosis through translational modulation of the p53-Mdm2 feedback loop

Insulin-like growth factor 1 receptor (IGF-1R) is important in cancer cell growth and survival and has been implicated in cancer pathophysiology and treatment. Here we report a novel function for IGF-1R in p53-dependent apoptotic response. We show that inhibition or loss of IGF-1R activity reduces translational synthesis of p53 and Mdm2 protein. Notably, IGF-1R inhibition increases p53 protein stability by reducing p53 ubiquitination and maintains p53 at low levels by decreasing p53 synthesis, thus rendering p53 insensitive to stabilization after DNA damage. The accumulation and apoptosis of DNA-damage–induced p53 is therefore reduced in Igf-1r−/− mouse embryonic fibroblasts or tumor cells treated with the IGF-1R inhibitor. Furthermore, we find that inhibition of IGF-1R reduces p53 and Mdm2 translation through a gene-specific mechanism mediated by the respective 5′ untranslated region of p53 and mdm2 messenger RNA. The eukaryotic translation initiation factor 4F complex is also involved in this translational inhibition. These results demonstrate an unexpected role for translational control by IGF-1R in p53-mediated apoptosis

Effects of Trehalose, Bovine Serum Albumin, and Sucrose, on the Integrity of the Plasma Membrane of Pseudosciaena crocea Semen after Cryopreservation

Cryopreservation and the effect of additives on the plasma membrane stability, motility, enzyme activity, membrane lipid composition, and ultrastructural injury of sperm of Pseudosciaena crocea, were examined in this study. Results indicated that the addition of trehalose (TH) and bovine serum albumin (BSA) provided significantly better results in the motility test compared to sucrose. Some BSA groups, showed significantly increased semen motility and effective enzyme activity. There were no significant differences between the cholesterol (CHO) composition for fresh sperm and cryopreserved sperm stored in 3 g/L BSA or 8.56 g/L TH+3 g/L BSA. Ultrastructural injury included damaged membrane, lost mitochondria, or broken flagella, whereas the majority of the freeze-thawed sperm remained morphologically normal. In conclusion, the addition of 3 g/L BSA and 8.56 g/L TH+3 g/L BSA significantly increased semen quality

A Kind of Change Management Method for Global Value Chain Optimization and Its Case Study

Any successful change in an organization requires an appropriate change management method and a process for involved staff and department to accept the change and become engaged in order to achieve its success. It is even more important and difficult to adopt a novel change management method to bring multiple organizations across the business value chain into the change implementation. This research does not focused on change management within a single organization but rather emphasizes a change management method, including an appropriate change framework, well-defined critical success factors (CSFs), and related tools for implementing change in multiple organizations. This article introduces one kind of change management method to support a process change through global value chain (GVC) in multiple organizations, and the method is used in a case study to achieve a successful change. In order to succeed in optimizing GVC performance, this research applies the proposed change management method to the case GVC, to support technical change by obtaining the staff's full commitment and engagement. The achieved results from the case study prove that successful change comes not only through technical solutions implemented in the problem process throughout the GVC but also through strong support and engagement from all organizations and involved staff. The proposed change management method not only helped the case GVC to implement change successfully but also can help the relevant multiple organizations to improve the GVC performance and add value by optimizing their problem process.©2021 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.fi=vertaisarvioitu|en=peerReviewed

DialogRE^C+: An Extension of DialogRE to Investigate How Much Coreference Helps Relation Extraction in Dialogs

Dialogue relation extraction (DRE) that identifies the relations between argument pairs in dialogue text, suffers much from the frequent occurrence of personal pronouns, or entity and speaker coreference. This work introduces a new benchmark dataset DialogRE^C+, introducing coreference resolution into the DRE scenario. With the aid of high-quality coreference knowledge, the reasoning of argument relations is expected to be enhanced. In DialogRE^C+ dataset, we manually annotate total 5,068 coreference chains over 36,369 argument mentions based on the existing DialogRE data, where four different coreference chain types namely speaker chain, person chain, location chain and organization chain are explicitly marked. We further develop 4 coreference-enhanced graph-based DRE models, which learn effective coreference representations for improving the DRE task. We also train a coreference resolution model based on our annotations and evaluate the effect of automatically extracted coreference chains demonstrating the practicality of our dataset and its potential to other domains and tasks.Comment: Accepted by NLPCC 202

Improving Factual Consistency of Text Summarization by Adversarially Decoupling Comprehension and Embellishment Abilities of LLMs

Despite the recent progress in text summarization made by large language models (LLMs), they often generate summaries that are factually inconsistent with original articles, known as "hallucinations" in text generation. Unlike previous small models (e.g., BART, T5), current LLMs make fewer silly mistakes but more sophisticated ones, such as imposing cause and effect, adding false details, overgeneralizing, etc. These hallucinations are challenging to detect through traditional methods, which poses great challenges for improving the factual consistency of text summarization. In this paper, we propose an adversarially DEcoupling method to disentangle the Comprehension and EmbellishmeNT abilities of LLMs (DECENT). Furthermore, we adopt a probing-based efficient training to cover the shortage of sensitivity for true and false in the training process of LLMs. In this way, LLMs are less confused about embellishing and understanding; thus, they can execute the instructions more accurately and have enhanced abilities to distinguish hallucinations. Experimental results show that DECENT significantly improves the reliability of text summarization based on LLMs

Pleiotropic effects of the twin-arginine translocation system on biofilm formation, colonization, and virulence in Vibrio cholerae

<p>Abstract</p> <p>Background</p> <p>The Twin-arginine translocation (Tat) system serves to translocate folded proteins, including periplasmic enzymes that bind redox cofactors in bacteria. The Tat system is also a determinant of virulence in some pathogenic bacteria, related to pleiotropic effects including growth, motility, and the secretion of some virulent factors. The contribution of the Tat pathway to <it>Vibrio cholerae </it>has not been explored. Here we investigated the functionality of the Tat system in <it>V. cholerae</it>, the etiologic agent of cholera.</p> <p>Results</p> <p>In <it>V. cholerae</it>, the <it>tatABC </it>genes function in the translocation of TMAO reductase. Deletion of the <it>tatABC </it>genes led to a significant decrease in biofilm formation, the ability to attach to HT-29 cells, and the ability to colonize suckling mouse intestines. In addition, we observed a reduction in the output of cholera toxin, which may be due to the decreased transcription level of the toxin gene in <it>tatABC </it>mutants, suggesting an indirect effect of the mutation on toxin production. No obvious differences in flagellum biosynthesis and motility were found between the <it>tatABC </it>mutant and the parental strain, showing a variable effect of Tat in different bacteria.</p> <p>Conclusion</p> <p>The Tat system contributes to the survival of <it>V. cholerae </it>in the environment and <it>in vivo</it>, and it may be associated with its virulence.</p