An M protein coiled coil unfurls and exposes its hydrophobic core to capture LL-37

Surface-associated, coiled-coil M proteins of Streptococcus pyogenes (Strep A) disable human immunity through interaction with select proteins. However, coiled coils lack features typical of protein-protein interaction sites, and it is therefore challenging to understand how M proteins achieve specific binding, for example, with the human antimicrobial peptide LL-37, which results in its neutralization. The crystal structure of a complex of LL-37 with M87 protein, an antigenic variant from a strain that is an emerging threat, revealed a novel interaction mode. The M87 coiled coil unfurled and asymmetrically exposed its hydrophobic core to capture LL-37. A single LL-37 molecule bound M87 in the crystal, but in solution recruited additional LL-37 molecules, consistent with a protein trap neutralization mechanism. The interaction mode visualized crystallographically was verified to contribute significantly to LL-37 resistance in an M87 Strep A strain, and was identified to be conserved in a number of other M protein types that are prevalent in human populations. Our results provide specific detail for therapeutic inhibition of LL-37 neutralization by M proteins.

The Microinteractive Order of Spirituality

The discourse of spirituality emphasizes personal, embodied experience. This emphasis can lead to a relatively individualized understanding of spirituality that neglects the fact that spirituality is practiced in groups and is based on the production of intersubjective spaces in which people learn together to look inward and experience transcendence. This chapter tracks the unique social order of vipassana meditation retreats, illustrating that meditation training is not merely psychological—it includes training in a new kind of social interaction mode. The community of practitioners in the meditation center is one of “collective solitude,” as practitioners are in close proximity to one another but avoid direct social engagement, helping one another to transcend the tendency to focus on the self as seen by others. Social spheres such as meditation groups, yoga, pilgrimage, or even mass prayer all resemble the collective solitude described in the context of vipassana meditation.

Correction: Freischem et al. Interaction Mode of the Novel Monobactam AIC499 Targeting Penicillin Binding Protein 3 of Gram-Negative Bacteria. Biomolecules 2021, 11, 1057

In the original article [...]

Characteristics of Vapor Based on Complex Networks in China

The uneven spatial distribution of stations providing precipitable water vapor (PWV) observations in China hinders the effective use of these data in data assimilation, nowcasting, and prediction. . In this study, we propose a complex network framework for exploring the topological structure and the collective behavior of PWV in mainland China. We used the Pearson correlation coefficient and transfer entropy to measure the linear and nonlinear relationships of PWV amongst different stations and to set up undirected and directed complex networks, respectively. Our findings revealed the statistical and geographical distribution of the variables influencing PWV networks and identified the vapor information source and sink stations. Specifically, the findings showed that the statistical and spatial distributions of the undirected and directed complex vapor networks in terms of degree and distance were similar to each other (the common interaction mode for vapor stations and their locations). The betweenness results displayed different features. The largest betweenness ratio for directed networks tended to be larger than that of undirected networks, implying the transfer of directed PWV networks was more efficient than that of undirected networks. The findings of this study are heuristic and will be useful for constructing the best strategy for the application of PWV data in applications such as vapor observational networks design and precipitation prediction.

Model Test on Mechanical and Deformation Property of a Geomembrane Surface Barrier for a High Rockfill Dam

The cushion of a geomembrane surface barrier of a high rockfill dam built on deep overburden is prone to crack and fail because of excessive flexural deformation. This study proposes a geomembrane surface barrier for a high rockfill dam on deep overburden. The proposed geomembrane surface barrier uses polyurethane bonded aggregates as the cushion material. The loading and deformation performance of the barrier system under uniform water pressure was investigated using a self-developed structure model test device. The mechanical and deformation property of each layer of the barrier, and the interaction mode between adjacent layers, were obtained through external videos and internal sensor monitoring. The results demonstrated that the polyurethane bonded aggregate cushion exhibited good adaptability to flexural deformation during the entire loading process and maintained good contact and coordinate deformation with the upper protective and the lower transition layers. The geomembrane surface barrier created using polyurethane bonded aggregates as the cushion material can adapt to the flexural deformation of a high rockfill dam surface on deep overburden.

Study on the host–guest complex of dicyclohexanocucurbit[6]uril and 2-phenylbenzimidazole, and its recognition effect toward Fe 3+

This paper has selected dicyclohexanocucurbit[6]uril (CyH 2 Q[6]) as the host and 2-phenylbenzimidazole ( G ) as the guest to investigate the host–guest interaction mode between CyH 2 Q[6] and G . Under acidic conditions, the complex was characterized using nuclear magnetic resonance, ultraviolet and fluorescence spectroscopy. The results show that the molecular ratio of CyH 2 Q[6] to G is 2 : 1. The crystals were cultured with ZnCl 2 as a structural inducer under acidic conditions and single crystal X-ray diffraction showed that the molecular ratio of CyH 2 Q[6] to G is 1 : 3. The G@CyH 2 Q[6] was used as a fluorescent probe to identify metal cations. The probe exhibits a good selective recognition effect toward Fe 3+ ions, which involves a reduced fluorescence intensity with a limit of detection of 1.321 × 10 –6 mol l –1 .

A Multitask Learning Model with Multiperspective Attention and Its Application in Recommendation

Training models to predict click and order targets at the same time. For better user satisfaction and business effectiveness, multitask learning is one of the most important methods in e-commerce. Some existing researches model user representation based on historical behaviour sequence to capture user interests. It is often the case that user interests may change from their past routines. However, multi-perspective attention has broad horizon, which covers different characteristics of human reasoning, emotions, perception, attention, and memory. In this paper, we attempt to introduce the multi-perspective attention and sequence behaviour into multitask learning. Our proposed method offers better understanding of user interest and decision. To achieve more flexible parameter sharing and maintaining the special feature advantage of each task, we improve the attention mechanism at the view of expert interactive. To the best of our knowledge, we firstly propose the implicit interaction mode, the explicit hard interaction mode, the explicit soft interaction mode, and the data fusion mode in multitask learning. We do experiments on public data and lab medical data. The results show that our model consistently achieves remarkable improvements to the state-of-the-art method.

Structural Basis of Inhibition of DCLK1 by Ruxolitinib

Given the functional attributes of Doublecortin-like kinase 1 (DCLK1) in tumor growth, invasion, metastasis, cell motility, and tumor stemness, it is emerging as a therapeutic target in gastrointestinal cancers. Although a series of specific or nonspecific ATP-competitive inhibitors were identified against DCLK1, different types of scaffolds that can be utilized for the development of highly selective inhibitors or structural understanding of binding specificities of the compounds remain limited. Here, we present our work to repurpose a Janus kinase 1 inhibitor, ruxolitinib as a DCLK1 inhibitor, showing micromolar binding affinity and inhibitory activity. Furthermore, to gain an insight into its interaction mode with DCLK1, a crystal structure of the ruxolitinib-complexed DCLK1 has been determined and analyzed. Ruxolitinib as a nonspecific DCLK1 inhibitor characterized in this work is anticipated to provide a starting point for the structure-guided discovery of selective DCLK1 inhibitors.