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  1. Abstract

    Membrane efflux pumps play a major role in bacterial multidrug resistance. The tripartite multidrug efflux pump system fromEscherichia coli, AcrAB-TolC, is a target for inhibition to lessen resistance development and restore antibiotic efficacy, with homologs in other ESKAPE pathogens. Here, we rationalize a mechanism of inhibition against the periplasmic adaptor protein, AcrA, using a combination of hydrogen/deuterium exchange mass spectrometry, cellular efflux assays, and molecular dynamics simulations. We define the structural dynamics of AcrA and find that an inhibitor can inflict long-range stabilisation across all four of its domains, whereas an interacting efflux substrate has minimal effect. Our results support a model where an inhibitor forms a molecular wedge within a cleft between the lipoyl and αβ barrel domains of AcrA, diminishing its conformational transmission of drug-evoked signals from AcrB to TolC. This work provides molecular insights into multidrug adaptor protein function which could be valuable for developing antimicrobial therapeutics.

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  2. Synopsis

    Many organisms exhibit collecting and gathering behaviors as a foraging and survival method. Benthic macroinvertebrates are classified as collector–gatherers due to their collection of particulate matter. Among these, the aquatic oligochaete Lumbriculus variegatus (California blackworms) demonstrates the ability to ingest both organic and inorganic materials, including microplastics. However, earlier studies have only qualitatively described their collecting behaviors for such materials. The mechanism by which blackworms consolidate discrete particles into a larger clump remains unexplored quantitatively. In this study, we analyze a group of blackworms in a large arena with an aqueous algae solution (organic particles) and find that their relative collecting efficiency is proportional to population size. We found that doubling the population size (N = 25–N = 50) results in a decrease in time to reach consolidation by more than half. Microscopic examination of individual blackworms reveals that both algae and microplastics physically adhere to the worm’s body and form clumps due to external mucus secretions by the worms. Our observations also indicate that this clumping behavior reduces the worm’s exploration of its environment, possibly due to thigmotaxis. To validate these observed biophysical mechanisms, we create an active polymer model of a worm moving in a field of particulate debris. We simulate its adhesive nature by implementing a short-range attraction between the worm and the nearest surrounding particles. Our findings indicate an increase in gathering efficiency when we add an attractive force between particles, simulating the worm’s mucosal secretions. Our work provides a detailed understanding of the complex mechanisms underlying the collecting–gathering behavior in L. variegatus, informing the design of bioinspired synthetic collector systems, and advances our understanding of the ecological impacts of microplastics on benthic invertebrates.

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  3. Synopsis

    A dog's nose differs from a human's in that air does not change direction but flows in a unidirectional path from inlet to outlet. Previous simulations showed that unidirectional flow through a dog’s complex nasal passageways creates stagnant zones of trapped air. We hypothesize that these zones give the dog a “physical memory,” which it may use to compare recent odors to past ones. In this study, we conducted experiments with our previously built Gaseous Recognition Oscillatory Machine Integrating Technology (GROMIT) and performed corresponding simulations in two dimensions. We compared three settings: a control setting that mimics the bidirectional flow of the human nose; a short-circuit setting where odors exit before reaching the sensors; and a unidirectional configuration using a dedicated inlet and outlet that mimics the dog’s nose. After exposure to odors, the sensors in the unidirectional setting showed the slowest return to their baseline level, indicative of memory effects. Simulations showed that both short-circuit and unidirectional flows created trapped recirculation zones, which slowed the release of odors from the chamber. In the future, memory effects such as the ones found here may improve the sensitivity and utility of electronic noses.

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  4. Abstract

    Dormancy is an adaptation to living in fluctuating environments. It allows individuals to enter a reversible state of reduced metabolic activity when challenged by unfavorable conditions. Dormancy can also influence species interactions by providing organisms with a refuge from predators and parasites. Here we test the hypothesis that, by generating a seed bank of protected individuals, dormancy can modify the patterns and processes of antagonistic coevolution. We conducted a factorially designed experiment where we passaged a bacterial host (Bacillus subtilis) and its phage (SPO1) in the presence versus absence of a seed bank consisting of dormant endospores. Owing in part to the inability of phages to attach to spores, seed banks stabilized population dynamics and resulted in minimum host densities that were 30-fold higher compared to bacteria that were unable to engage in dormancy. By supplying a refuge to phage-sensitive strains, we show that seed banks retained phenotypic diversity that was otherwise lost to selection. Dormancy also stored genetic diversity. After characterizing allelic variation with pooled population sequencing, we found that seed banks retained twice as many host genes with mutations, whether phages were present or not. Based on mutational trajectories over the course of the experiment, we demonstrate that seed banks can dampen bacteria-phage coevolution. Not only does dormancy create structure and memory that buffers populations against environmental fluctuations, it also modifies species interactions in ways that can feed back onto the eco-evolutionary dynamics of microbial communities.

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  5. Abstract

    Many organisms utilize group aggregation as a method for survival. The freshwater oligochaete, Lumbriculus variegatus (California blackworms) form tightly entangled structures, or worm “blobs”, that have adapted to survive in extremely low levels of dissolved oxygen (DO). Individual blackworms adapt to hypoxic environments through respiration via their mucous body wall and posterior ciliated hindgut, which they wave above them. However, the change in collective behavior at different levels of DO is not known. Using a closed-loop respirometer with flow, we discover that the relative tail reaching activity flux in low DO is ∼75x higher than in the high-DO condition. Additionally, when flow rate is increased to suspend the worm blobs upward, we find that the average exposed surface area of a blob in low DO is ∼1.4x higher than in high DO. Furthermore, we observe emergent properties that arise when a worm blob is exposed to extreme DO levels. We demonstrate that internal mechanical stress is generated when worm blobs are exposed to high DO levels, allowing them to be physically lifted off from the bottom of a conical container using a serrated endpiece. Our results demonstrate how both collective behavior and the emergent generation of internal mechanical stress in worm blobs change to accommodate differing levels of oxygen. From an engineering perspective, this could be used to model and simulate swarm robots, self-assembly structures, or soft material entanglements.

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  6. Abstract

    Regulation of membrane receptor mobility tunes cellular response to external signals, such as in binding of B cell receptors (BCR) to antigen, which initiates signaling. However, whether BCR signaling is regulated by BCR mobility, and what factors mediate this regulation, are not well understood. Here we use single molecule imaging to examine BCR movement during signaling activation and a novel machine learning method to classify BCR trajectories into distinct diffusive states. Inhibition of actin dynamics downstream of the actin nucleating factors, Arp2/3 and formin, decreases BCR mobility. Constitutive loss or acute inhibition of the Arp2/3 regulator, N-WASP, which is associated with enhanced signaling, increases the proportion of BCR trajectories with lower diffusivity. Furthermore, loss of N-WASP reduces the diffusivity of CD19, a stimulatory co-receptor, but not that of FcγRIIB, an inhibitory co-receptor. Our results implicate a dynamic actin network in fine-tuning receptor mobility and receptor-ligand interactions for modulating B cell signaling.

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  7. Robots have components that work together to accomplish a task. Colloids are particles, usually less than 100 µm, that are small enough that they do not settle out of solution. Colloidal robots are particles capable of functions such as sensing, computation, communication, locomotion and energy management that are all controlled by the particle itself. Their design and synthesis is an emerging area of interdisciplinary research drawing from materials science, colloid science, self-assembly, robophysics and control theory. Many colloidal robot systems approach synthetic versions of biological cells in autonomy and may find ultimate utility in bringing these specialized functions to previously inaccessible locations. This Perspective examines the emerging literature and highlights certain design principles and strategies towards the realization of colloidal robots. 
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    Free, publicly-accessible full text available August 24, 2024
  8. Contact planning is crucial to the locomotion performance of robots: to properly self-propel forward, it is not only important to determine the sequence of internal shape changes (e.g., body bending and limb shoulder joint oscillation) but also the sequence by which contact is made and broken between the mechanism and its environment. Prior work observed that properly coupling contact patterns and shape changes allows for computationally tractable gait design and efficient gait performance. The state of the art, however, made assumptions, albeit motivated by biological observation, as to how contact and shape changes can be coupled. In this paper, we extend the geometric mechanics (GM) framework to design contact patterns. Specifically, we introduce the concept of “contact space” to the GM framework. By establishing the connection between velocities in shape and position spaces, we can estimate the benefits of each contact pattern change and therefore optimize the sequence of contact patterns. In doing so, we can also analyze how a contact pattern sequence will respond to perturbations. We apply our framework to sidewinding robots and enable (1) effective locomotion direction control and (2) robust locomotion performance as the spatial resolution decreases. We also apply our framework to a hexapod robot with two back-bending joints and show that we can simplify existing hexapod gaits by properly reducing the number of contact state switches (during a gait cycle) without significant loss of locomotion speed. We test our designed gaits with robophysical experiments, and we obtain good agreement between theory and experiments. 
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    Free, publicly-accessible full text available August 11, 2024
  9. Abstract Recent observations of wingless animals, including jumping nematodes, springtails, insects, and wingless vertebrates like geckos, snakes, and salamanders, have shown that their adaptations and body morphing are essential for rapid self-righting and controlled landing. These skills can reduce the risk of physical damage during collision, minimize recoil during landing, and allow for a quick escape response to minimize predation risk. The size, mass distribution, and speed of an animal determine its self-righting method, with larger animals depending on the conservation of angular momentum and smaller animals primarily using aerodynamic forces. Many animals falling through the air, from nematodes to salamanders, adopt a skydiving posture while descending. Similarly, plant seeds such as dandelions and samaras are able to turn upright in mid-air using aerodynamic forces and produce high decelerations. These aerial capabilities allow for a wide dispersal range, low-impact collisions, and effective landing and settling. Recently, small robots that can right themselves for controlled landings have been designed based on principles of aerial maneuvering in animals. Further research into the effects of unsteady flows on self-righting and landing in small arthropods, particularly those exhibiting explosive catapulting, could reveal how morphological features, flow dynamics, and physical mechanisms contribute to effective mid-air control. More broadly, studying apterygote (wingless insects) landing could also provide insight into the origin of insect flight. These research efforts have the potential to lead to the bio-inspired design of aerial micro-vehicles, sports projectiles, parachutes, and impulsive robots that can land upright in unsteady flow conditions. 
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    Free, publicly-accessible full text available August 8, 2024