HLH-30/TFEB-mediated autophagy functions in a cell-autonomous manner for epithelium intrinsic cellular defense against bacterial pore-forming toxin in C. elegans

Autophagy is an evolutionarily conserved intracellular system that maintains cellular homeostasis by degrading and recycling damaged cellular components. The transcription factor HLH-30/TFEB-mediated autophagy has been reported to regulate tolerance to bacterial infection, but less is known about the bona fide bacterial effector that activates HLH-30 and autophagy. Here, we reveal that bacterial membrane pore-forming toxin (PFT) induces autophagy in an HLH-30-dependent manner in Caenorhabditis elegans. Moreover, autophagy controls the susceptibility of animals to PFT toxicity through xenophagic degradation of PFT and repair of membrane-pore cell-autonomously in the PFT-targeted intestinal cells in C. elegans. These results demonstrate that autophagic pathways and autophagy are induced partly at the transcriptional level through HLH-30 activation and are required to protect metazoan upon PFT intoxication. Together, our data show a new and powerful connection between HLH-30-mediated autophagy and epithelium intrinsic cellular defense against the single most common mode of bacterial attack in vivo

Macroscopic Quantum Mechanics in a Classical Spacetime

We apply the many-particle Schrödinger-Newton equation, which describes the coevolution of a many-particle quantum wave function and a classical space-time geometry, to macroscopic mechanical objects. By averaging over motions of the objects’ internal degrees of freedom, we obtain an effective Schrödinger-Newton equation for their centers of mass, which can be monitored and manipulated at quantum levels by state-of-the-art optomechanics experiments. For a single macroscopic object moving quantum mechanically within a harmonic potential well, its quantum uncertainty is found to evolve at a frequency different from its classical eigenfrequency—with a difference that depends on the internal structure of the object—and can be observable using current technology. For several objects, the Schrödinger-Newton equation predicts semiclassical motions just like Newtonian physics, yet quantum uncertainty cannot be transferred from one object to another

Tango: rethinking quantization for graph neural network training on GPUs

Graph Neural Networks (GNNs) are becoming increasingly popular due to their superior performance in critical graph-related tasks. While quantization is widely used to accelerate GNN computation, quantized training faces unprecedented challenges. Current quantized GNN training systems often have longer training times than their full-precision counterparts for two reasons: (i) addressing the accuracy challenge leads to excessive overhead, and (ii) the optimization potential exposed by quantization is not adequately leveraged. This paper introduces Tango which re-thinks quantization challenges and opportunities for graph neural network training on GPUs with three contributions: Firstly, we introduce efficient rules to maintain accuracy during quantized GNN training. Secondly, we design and implement quantization-aware primitives and inter-primitive optimizations that can speed up GNN training. Finally, we integrate Tango with the popular Deep Graph Library (DGL) system and demonstrate its superior performance over state-of-the-art approaches on various GNN models and datasets

Evolving MCDM Applications Using Hybrid Expert-Based ISM and DEMATEL Models: An Example of Sustainable Ecotourism

Ecological degradation is an escalating global threat. Increasingly, people are expressing awareness and priority for concerns about environmental problems surrounding them. Environmental protection issues are highlighted. An appropriate information technology tool, the growing popular social network system (virtual community, VC), facilitates public education and engagement with applications for existent problems effectively. Particularly, the exploration of related involvement behavior of VC member engagement is an interesting topic. Nevertheless, member engagement processes comprise interrelated sub-processes that reflect an interactive experience within VCs as well as the value co-creation model. To address the top-focused ecotourism VCs, this study presents an application of a hybrid expert-based ISM model and DEMATEL model based on multi-criteria decision making tools to investigate the complex multidimensional and dynamic nature of member engagement. Our research findings provide insightful managerial implications and suggest that the viral marketing of ecotourism protection is concerned with practitioners and academicians alike

Vocal cord dysfunction diagnosed by four-dimensional dynamic volume computed tomography in patients with difficult-to-treat asthma: A case series

Patients with asthma may also have vocal cord dysfunction (VCD), which leads to poor control of the asthma. Once patients are diagnosed with difficult-to-treat asthma with poor control, VCD should be excluded or treated accordingly. The gold standard for diagnosis of VCD is to perform a laryngoscopy. However, this procedure is invasive and may not be suitable for patients with difficult-to-treat asthma. Four-dimensional (4D) dynamic volume computed tomography (CT) is a noninvasive method for quantification of laryngeal movement, and can serve as an alternative for the diagnosis of VCD. Herein, we present a series of five cases with difficult-to-treat asthma patients who were diagnosed with VCD by 4D dynamic volume CT. Clinicians should be alert to the possibility of VCD when poor control is noted in patients with asthma. Early diagnosis by noninvasive 4D dynamic volume CT can decrease excessive doses of inhaled corticosteroids

WWP-1 Is a Novel Modulator of the DAF-2 Insulin-Like Signaling Network Involved in Pore-Forming Toxin Cellular Defenses in Caenorhabditis elegans

Pore-forming toxins (PFTs) are the single largest class of bacterial virulence factors. The DAF-2 insulin/insulin-like growth factor-1 signaling pathway, which regulates lifespan and stress resistance in Caenorhabditis elegans, is known to mutate to resistance to pathogenic bacteria. However, its role in responses against bacterial toxins and PFTs is as yet unexplored. Here we reveal that reduction of the DAF-2 insulin-like pathway confers the resistance of Caenorhabditis elegans to cytolitic crystal (Cry) PFTs produced by Bacillus thuringiensis. In contrast to the canonical DAF-2 insulin-like signaling pathway previously defined for aging and pathogenesis, the PFT response pathway diverges at 3-phosphoinositide-dependent kinase 1 (PDK-1) and appears to feed into a novel insulin-like pathway signal arm defined by the WW domain Protein 1 (WWP-1). In addition, we also find that WWP-1 not only plays an important role in the intrinsic cellular defense (INCED) against PFTs but also is involved in innate immunity against pathogenic bacteria Pseudomonas aeruginosa and in lifespan regulation. Taken together, our data suggest that WWP-1 and DAF-16 function in parallel within the fundamental DAF-2 insulin/IGF-1 signaling network to regulate fundamental cellular responses in C. elegans