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Abstract Studies of folded-to-misfolded transitions using model protein systems reveal a range of unfolding needed for exposure of amyloid-prone regions for subsequent fibrillization. Here, we probe the relationship between unfolding and aggregation for glaucoma-associated myocilin. Mutations within the olfactomedin domain of myocilin (OLF) cause a gain-of-function, namely cytotoxic intracellular aggregation, which hastens disease progression. Aggregation by wild-type OLF (OLF^WT) competes with its chemical unfolding, but only below the threshold where OLF loses tertiary structure. Representative moderate (OLF^D380A) and severe (OLF^I499F) disease variants aggregate differently, with rates comparable to OLF^WTin initial stages of unfolding, and variants adopt distinct partially folded structures seen along the OLF^WTurea-unfolding pathway. Whether initiated with mutation or chemical perturbation, unfolding propagates outward to the propeller surface. In sum, for this large protein prone to amyloid formation, the requirement for a conformational change to promote amyloid fibrillization leads to direct competition between unfolding and aggregation. 

Synopsis We investigate how the Helobdella sp. freshwater leeches capture and consume Lumbriculus variegatus blackworms despite the blackworm’s ultrafast helical swimming escape reflex and ability to form large tangled “blobs.” We describe a spiral “entombment” predation strategy, where Helobdellid leeches latch onto blackworms with their anterior sucker and envelop them in a spiral cocoon. Quantitative analysis shows that larger leeches succeed more often in entombing prey, while longer worms tend to escape. The rate of spiral contraction correlates with entombment outcomes, with slower rates associated with success. These insights highlight the complex interactions between predator and prey in freshwater ecosystems, providing new perspectives on ecological adaptability and predator-prey dynamics. 

Synopsis Dimensionless numbers have long been used in comparative biomechanics to quantify competing scaling relationships and connect morphology to animal performance. While common in aerodynamics, few relate the biomechanics of the organism to the forces produced on the environment during flight. We discuss the Weis-Fogh number, N, as a dimensionless number specific to flapping flight, which describes the resonant properties of an insect and resulting tradeoffs between energetics and control. Originally defined by Torkel Weis-Fogh in his seminal 1973 paper, N measures the ratio of peak inertial to aerodynamic torque generated by an insect over a wingbeat. In this perspectives piece, we define N for comparative biologists and describe its interpretations as a ratio of torques and as the width of an insect’s resonance curve. We then discuss the range of N realized by insects and explain the fundamental tradeoffs between an insect’s aerodynamic efficiency, stability, and responsiveness that arise as a consequence of variation in N, both across and within species. N is therefore an especially useful quantity for comparative approaches to the role of mechanics and aerodynamics in insect flight. 

Synopsis Insects exhibit remarkable adaptability in their locomotive strategies in diverse environments, a crucial trait for foraging, survival, and predator avoidance. Microvelia americana, tiny 2–3 mm insects that adeptly walk on water surfaces, exemplify this adaptability by using the alternating tripod gait in both aquatic and terrestrial terrains. These insects commonly inhabit low-flow ponds and streams cluttered with natural debris like leaves, twigs, and duckweed. Using high-speed imaging and pose-estimation software, we analyze M. americana movement on water, sandpaper (simulating land), and varying duckweed densities (10%, 25%, and 50% coverage). Our results reveal M. americana maintain consistent joint angles and strides of their upper and hind legs across all duckweed coverages, mirroring those seen on sandpaper. Microvelia americana adjust the stride length of their middle legs based on the amount of duckweed present, decreasing with increased duckweed coverage and at 50% duckweed coverage, their middle legs’ strides closely mimic their strides on sandpaper. Notably, M. americana achieve speeds up to 56 body lengths per second on the deformable surface of water, nearly double those observed on sandpaper and duckweed, which are rough, heterogeneous surfaces. This study highlights M. americana’s ecological adaptability, setting the stage for advancements in amphibious robotics that emulate their unique tripod gait for navigating complex terrains. 

Synopsis The evolution of flight in an early winged insect ancestral lineage is recognized as a key adaptation explaining the unparalleled success and diversification of insects. Subsequent transitions and modifications to flight machinery, including secondary reductions and losses, also play a central role in shaping the impacts of insects on broadscale geographic and ecological processes and patterns in the present and future. Given the importance of insect flight, there has been a centuries-long history of research and debate on the evolutionary origins and biological mechanisms of flight. Here, we revisit this history from an interdisciplinary perspective, discussing recent discoveries regarding the developmental origins, physiology, biomechanics, and neurobiology and sensory control of flight in a diverse set of insect models. We also identify major outstanding questions yet to be addressed and provide recommendations for overcoming current methodological challenges faced when studying insect flight, which will allow the field to continue to move forward in new and exciting directions. By integrating mechanistic work into ecological and evolutionary contexts, we hope that this synthesis promotes and stimulates new interdisciplinary research efforts necessary to close the many existing gaps about the causes and consequences of insect flight evolution. 

Abstract BackgroundRepolarization alternans, defined as period-2 oscillation in the repolarization phase of the action potentials, is one of the cornerstones of cardiac electrophysiology as it provides a mechanistic link between cellular dynamics and ventricular fibrillation (VF). Theoretically, higher-order periodicities (e.g., period-4, period-8,…) are expected but have very limited experimental evidence. MethodsWe studied explanted human hearts, obtained from the recipients of heart transplantation at the time of surgery, using optical mapping technique with transmembrane voltage-sensitive fluorescent dyes. The hearts were stimulated at an increasing rate until VF was induced. The signals recorded from the right ventricle endocardial surface just before the induction of VF and in the presence of 1:1 conduction were processed using the Principal Component Analysis and a combinatorial algorithm to detect and quantify higher-order dynamics. ResultsA prominent and statistically significant 1:4 peak (corresponding to period-4 dynamics) was seen in three of the six studied hearts. Local analysis revealed the spatiotemporal distribution of higher-order periods. Period-4 was localized to temporally stable islands. Higher-order oscillations (period-5, 6, and 8) were transient and primarily occurred in arcs parallel to the activation isochrones. DiscussionWe present evidence of higher-order periodicities and the co-existence of such regions with stable non-chaotic areas in ex-vivo human hearts before VF induction. This result is consistent with the period-doubling route to chaos as a possible mechanism of VF initiation, which complements the concordant to discordant alternans mechanism. The presence of higher-order regions may act as niduses of instability that can degenerate into chaotic fibrillation. 

Synopsis The air–water interface of the planet’s water bodies, such as ponds, lakes, and streams, presents an uncertain ecological niche with predatory threats from above and below. As Microvelia americana move across the water surface in small ponds, they face potential injury from attacks by birds, fish, and underwater invertebrates. Thus, our study investigates the effects of losing individual or pairs of tarsi on M. americana’s ability to walk on water. Removal of both hind tarsi causes M. americana to rock their bodies (yaw) while running across the water surface at $$\pm 19^{\circ }$$, compared to $$\pm 7^{\circ }$$ in nonablated specimens. This increase in yaw, resulting from the removal of hind tarsi, indicates that M. americana use their hind legs as “rudders” to regulate yaw, originating from the contralateral middle legs’ strokes on the water’s surface through an alternating tripod gait. Ablation of the ipsilateral middle and hind tarsi disrupts directionality, making M. americana turn in the direction of their intact limbs. This loss of directionality does not occur with the removal of contralateral middle and hind tarsi. However, M. americana lose their ability to use the alternating tripod gait to walk on water on the day of contralateral ablation. Remarkably, by the next day, M. americana adapt and regain the ability to walk on water using the alternating tripod gait. Our findings elucidate the specialized leg dynamics within the alternating tripod gait of M. americana, and their adaptability to tarsal loss. This research could guide the development and design strategies of small, adaptive, and resilient micro-robots that can adapt to controller malfunction or actuator damage for walking on water and terrestrial surfaces. 

Abstract Cosmic reionization is likely driven by UV starlight emanating from the first generations of galaxies. A galaxy’s UV escape fraction, or the fraction of photons escaping from the galaxy, is useful to quantify its contribution to reionization. However, the UV escape fraction is notoriously difficult to predict due to local environment dependency and variability over time. Using data from the Renaissance Simulations, we attempt to make predictions about the impact of the first stars and galaxies on their environments. We present a time-independent classification model using a general artificial neural network architecture to predict the UV escape fraction given other galaxy properties—namely halo mass, stellar mass, redshift, star formation rate, lookback time, and gas fraction. We find our validation accuracy to be approximately 50%–65%, depending on the data set size from each zoom-in region of the Renaissance Simulations. 

Abstract Since taking flight, insects have undergone repeated evolutionary transitions between two seemingly distinct flight modes^1–3. Some insects neurally activate their muscles synchronously with each wingstroke. However, many insects have achieved wingbeat frequencies beyond the speed limit of typical neuromuscular systems by evolving flight muscles that are asynchronous with neural activation and activate in response to mechanical stretch^2–8. These modes reflect the two fundamental ways of generating rhythmic movement: time-periodic forcing versus emergent oscillations from self-excitation^8–10. How repeated evolutionary transitions have occurred and what governs the switching between these distinct modes remain unknown. Here we find that, despite widespread asynchronous actuation in insects across the phylogeny^3,6, asynchrony probably evolved only once at the order level, with many reversions to the ancestral, synchronous mode. A synchronous moth species, evolved from an asynchronous ancestor, still preserves the stretch-activated muscle physiology. Numerical and robophysical analyses of a unified biophysical framework reveal that rather than a dichotomy, these two modes are two regimes of the same dynamics. Insects can transition between flight modes across a bridge in physiological parameter space. Finally, we integrate these two actuation modes into an insect-scale robot^11–13that enables transitions between modes and unlocks a new self-excited wingstroke strategy for engineered flight. Together, this framework accounts for repeated transitions in insect flight evolution and shows how flight modes can flip with changes in physiological parameters. 

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.