The ESKAPE mobilome contributes to the spread of antimicrobial resistance and CRISPR-mediated conflict between mobile genetic elements

Mobile genetic elements (MGEs) mediate the shuffling of genes among organisms. They contribute to the spread of virulence and antibiotic resistance genes in human pathogens, including the particularly problematic group of ESKAPE pathogens, such as Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter sp. Here, we performed the first systematic analysis of MGEs, including plasmids, prophages, and integrative and conjugative/mobilizable elements (ICEs/IMEs), in the ESKAPE pathogens. We characterized over 1700 complete ESKAPE genomes and found that different MGE types are asymmetrically distributed across these pathogens. While some MGEs are capable of exchanging DNA beyond the genus (and phylum) barrier, horizontal gene transfer (HGT) is mainly restricted by phylum or genus. We further observed that most genes on MGEs have unknown functions and show intricate distribution patterns. Moreover, AMR genes and anti-CRISPRs are overrepresented in the ESKAPE mobilome. Our results also underscored species-specific trends shaping the number of MGEs, AMR, and virulence genes across pairs of conspecific ESKAPE genomes with and without CRISPR-Cas systems. Finally, we found that CRISPR targets vary according to MGE type: while plasmid CRISPRs almost exclusively target other plasmids, ICEs/IME CRISPRs preferentially target ICEs/IMEs and prophages. Overall, our study highlights the general importance of the ESKAPE mobilome in contributing to the spread of AMR and mediating conflict among MGEs.

Is the Imitative Competence an Asymmetrically Distributed Function?

This study reconsiders behavioral and functional data from studies investigating the anatomical imitation (AI) and the related mental rotation (MR) competence, carried out by our group in healthy subjects, with intact interhemispheric connections, and in split-brain patients, completely or partially lacking callosal connections. The results strongly point to the conclusion that AI and MR competence requires interhemispheric communication, mainly occurring through the corpus callosum, which is the largest white matter structure in the human brain. The results are discussed in light of previous studies and of future implications.

Analysis of Asymmetrical Deformation of Surface and Oblique Pipeline Caused by Shield Tunneling along Curved Section

The deformation of existing pipelines caused by the tunneling of a shield machine along curved sections has not been sufficiently researched, and a corresponding theoretical prediction formula is lacking. This paper derives a prediction formula for the deformation of an existing pipeline caused by shield machine tunneling along a curved section. Further, a finite difference model (FDM) corresponding to an actual project is built. Finally, the deformation of the surface and existing pipelines caused by shield machine tunneling along the curved section is analyzed. The research results show that the results of theoretical prediction, FDM calculation, and field monitoring data are consistent. In addition, the deformation of the surface and the existing pipeline are asymmetrically distributed when the shield machine tunnels along the curve section instead of symmetrically distributed (for straight line segment). When the pipeline is perpendicular to the tunnel axis, the maximum deformation position of the existing pipeline deviates from the tunnel axis by about 0.5 times the tunnel radius. In addition, as the angle β between the pipeline axis and the tunnel axis increases, the maximum deformation position of the pipeline gradually approaches the tunnel axis.

Effect of Thickness Stretching on Bending and Free Vibration Behaviors of Functionally Graded Graphene Reinforced Composite Plates

The focus of this paper is the effect of thickness stretching on the static and dynamic behaviors of functionally graded graphene reinforced composite (FG-GRC) plates. The bending and free vibration behaviors of FG-GRC plates under simply supported conditions are studied based on two plate theories, with or without taking into account the thickness stretching effect, respectively, and the effect of thickness stretching on FG-GRC plates is analyzed by comparing the calculated results of the two types of plate theories. The properties of composite materials are estimated by the modified Halpin-Tsai model and rule of mixture, Hamilton’s principle is used to construct its governing equation, and the Navier solution method is used to find the closed solution. The numerical results show that the effect of thickness stretching depends mainly on the transverse anisotropy of the FG-GRC plates, and the FG-GRC plates are most significantly affected by the thickness stretching when the graphene nanoplatelets (GPLs) are asymmetrically distributed, and the effect of thickness stretching tends to increase as the total number of layers and the weight fraction of GPLs increase.

A New Quantile Regression Model and Its Diagnostic Analytics for a Weibull Distributed Response with Applications

Standard regression models focus on the mean response based on covariates. Quantile regression describes the quantile for a response conditioned to values of covariates. The relevance of quantile regression is even greater when the response follows an asymmetrical distribution. This relevance is because the mean is not a good centrality measure to resume asymmetrically distributed data. In such a scenario, the median is a better measure of the central tendency. Quantile regression, which includes median modeling, is a better alternative to describe asymmetrically distributed data. The Weibull distribution is asymmetrical, has positive support, and has been extensively studied. In this work, we propose a new approach to quantile regression based on the Weibull distribution parameterized by its quantiles. We estimate the model parameters using the maximum likelihood method, discuss their asymptotic properties, and develop hypothesis tests. Two types of residuals are presented to evaluate the model fitting to data. We conduct Monte Carlo simulations to assess the performance of the maximum likelihood estimators and residuals. Local influence techniques are also derived to analyze the impact of perturbations on the estimated parameters, allowing us to detect potentially influential observations. We apply the obtained results to a real-world data set to show how helpful this type of quantile regression model is.

Glycocalyx Curving the Membrane: Forces Emerging from the Cell Exterior

Morphological transitions are typically attributed to the actions of proteins and lipids. Largely overlooked in membrane shape regulation is the glycocalyx, a pericellular membrane coat that resides on all cells in the human body. Comprised of complex sugar polymers known as glycans as well as glycosylated lipids and proteins, the glycocalyx is ideally positioned to impart forces on the plasma membrane. Large, unstructured polysaccharides and glycoproteins in the glycocalyx can generate crowding pressures strong enough to induce membrane curvature. Stress may also originate from glycan chains that convey curvature preference on asymmetrically distributed lipids, which are exploited by binding factors and infectious agents to induce morphological changes. Through such forces, the glycocalyx can have profound effects on the biogenesis of functional cell surface structures as well as the secretion of extracellular vesicles. In this review, we discuss recent evidence and examples of these mechanisms in normal health and disease.

Phase Separation and Mechanical Forces in Regulating Asymmetric Cell Division of Neural Stem Cells

Asymmetric cell division (ACD) of neural stem cells and progenitors not only renews the stem cell population but also ensures the normal development of the nervous system, producing various types of neurons with different shapes and functions in the brain. One major mechanism to achieve ACD is the asymmetric localization and uneven segregation of intracellular proteins and organelles into sibling cells. Recent studies have demonstrated that liquid-liquid phase separation (LLPS) provides a potential mechanism for the formation of membrane-less biomolecular condensates that are asymmetrically distributed on limited membrane regions. Moreover, mechanical forces have emerged as pivotal regulators of asymmetric neural stem cell division by generating sibling cell size asymmetry. In this review, we will summarize recent discoveries of ACD mechanisms driven by LLPS and mechanical forces.

Extreme precision in rhythmic interaction is enabled by role-optimized sensorimotor coupling: analysis and modelling of West African drum ensemble music

Human social interactions often involve carefully synchronized behaviours. Musical performance in particular features precise timing and depends on the differentiation and coordination of musical/social roles. Here, we study the influence of musical/social roles, individual musicians and different ensembles on rhythmic synchronization in Malian drum ensemble music, which features synchronization accuracy near the limits of human performance. We analysed 72 recordings of the same piece performed by four trios, in which two drummers in each trio systematically switched roles (lead versus accompaniment). Musical role, rather than individual or group differences, is the main factor influencing synchronization accuracy. Using linear causal modelling, we found a consistent pattern of bi-directional couplings between players, in which the direction and strength of rhythmic adaptation is asymmetrically distributed across musical roles. This differs from notions of musical leadership, which assume that ensemble synchronization relies predominantly on a single dominant personality and/or musical role. We then ran simulations that varied the direction and strength of sensorimotor coupling and found that the coupling pattern used by the Malian musicians affords nearly optimal synchronization. More broadly, our study showcases the importance of ecologically valid and culturally diverse studies of human behaviour. This article is part of the theme issue ‘Synchrony and rhythm interaction: from the brain to behavioural ecology’.

Variable Stiffness Design and Analysis of Flexure Hinge Based on ID-LEJ

In recent years, compliant mechanisms have attracted more and more attention of scholars at home and abroad, and achieved rapid development. The introduction of flexible variable stiffness design in flexible mechanism can not only improve the safety of human-computer interaction, but also improve the adaptability of the machine. Because the ID-LEJ (Inside-Deployed Lamina Emergent Joint) is a kind of LEMs and has very good bending performance. In this paper, the rotary ID-LEJ flexure hinge is proposed based on ID-LEJ hinge, to maximize the bending capacity of the hinge. In order to realize variable stiffness of rotary ID-LEJ, four sliders are arranged in the rotary ID-LEJ to change the stiffness of the hinge. The variable stiffness of the hinge is analyzed by Equivalent system and Finite element analysis. When the slider is symmetrically divided (yl1=yl2=yr1=yr2) the bending equivalent constant of the variable stiffness hinge varies continuously from 30.8 n · mm / rad ∼ 38.2n · mm / rad. And when the slider is asymmetrically distributed (yl1=yl2≠yr1=yr2) The bending equivalent constant of the variable stiffness hinge varies continuously from 30.8n · mm / rad to 34.2 · mm / rad. The results show that the variable stiffness performance is very flexible and stable.

AQPX-cluster aquaporins and aquaglyceroporins are asymmetrically distributed in trypanosomes

Major Intrinsic Proteins (MIPs) are membrane channels that permeate water and other small solutes. Some trypanosomatid MIPs mediate the uptake of antiparasitic compounds, placing them as potential drug targets. However, a thorough study of the diversity of these channels is still missing. Here we place trypanosomatid channels in the sequence-function space of the large MIP superfamily through a sequence similarity network. This analysis exposes that trypanosomatid aquaporins integrate a distant cluster from the currently defined MIP families, here named aquaporin X (AQPX). Our phylogenetic analyses reveal that trypanosomatid MIPs distribute exclusively between aquaglyceroporin (GLP) and AQPX, being the AQPX family expanded in the Metakinetoplastina common ancestor before the origin of the parasitic order Trypanosomatida. Synteny analysis shows how African trypanosomes specifically lost AQPXs, whereas American trypanosomes specifically lost GLPs. AQPXs diverge from already described MIPs on crucial residues. Together, our results expose the diversity of trypanosomatid MIPs and will aid further functional, structural, and physiological research needed to face the potentiality of the AQPXs as gateways for trypanocidal drugs.