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One of the common hydrotherapeutic exercises is walking in water because buoyancy reduces joint loading and increases mobility for a patient. The fluid drag forces (the forces that act on the person from the fluid in the direction opposing the direction of motion) cause changes in muscle activations, as walking in water changes the forces that act on the leg compared with overground walking. Here, through a series of numerical simulations, we quantify how the flow forces that act on the leg due to its motion in water change over a walking gait cycle. We show that besides drag forces that act on the walking legs and peak when the leg is accelerated forward, relatively large lateral forces (in the direction perpendicular to the direction of motion) also act on the leg. These forces are caused by the rapid acceleration of the opposite leg when the two legs are close, creating an asymmetric pressure distribution around the leg. These results are unexpected and could have significant implications for designing hydrotherapeutic plans for patients by considering the lateral forces besides the drag forces that act on the body while walking in water. 

Summary Animals must flexibly respond to environmental stimuli to survive, and optimal responses critically depend on the organism’s current needs. Many organisms have evolved both cell-intrinsic and intertissue signaling pathways that integrate metabolic status. However, how this information is encoded in molecular signals is currently not well understood. Here we show that the nematodeC. elegansemploys lipidated neurohormones that combine the neurotransmitter octopamine and fat metabolism-derived building blocks to relay information about lipid metabolic status and drive inhibition of aversive olfactory responses during food removal. Using targeted metabolomics, we show that lipidated neurohormone synthesis requires the carboxylesterase CEST-2.1, which links octopamine-glucosides with endogenous methyl-branched or diet-derived cyclopropane fatty acids that act as agonists of the nuclear receptor and master regulator of fat metabolism, NHR-49/PPARα. Loss ofcest-2.1,loss of bacterial cyclopropane fatty acid production, or loss of endogenous biosynthesis of the methyl-branched fatty acid substrates of CEST-2.1 mimics the behavioral responses of animals lacking octopamine, indicating that regulation of neurotransmitter-dependent behavior is linked to the coordination of fat metabolism via NHR-49/PPARα. Biosynthesis and subsequent neuromodulation via lipidated neurohormone relies on an intertissue trafficking pathway in which octopamine is shuttled first into the intestine where it is chemically modified, which is likely followed by neuronal import and intracellular hydrolysis to finally release free octopamine. We propose that esterase-dependent synthesis and subsequent hydrolysis of lipidated neurohormones represents a chemical encoding mechanism by which animals integrate information from neurotransmitter signaling and lipid homeostasis to direct appropriate behaviors. 

A thorough understanding of the nature and pattern of intermolecular interactions in molecular aggregates and crystals is a prerequisite for the design of the next generation of functional materials. In systems with multiple, symmetrically equivalent molecules per unit cell, each excited state of the isolated molecule splits into several Davydov components that appear in the absorption spectra in up to three orthogonally polarized transitions. In this work, a Frenkel–Holstein Hamiltonian is adopted to simulate the vibronic structure of the Davydov components in aggregates and crystals with up to four molecules per unit cell, where electrostatic intermolecular interactions define either 1D or 2D structures. Analysis shows that vibronic signatures report directly on the electronic couplings that contribute to the Davydov splitting and the exciton band shapes. Specifically, the vibronic signature of a given Davydov component is solely determined by its free excitonic shift. For crystals with two molecules per unit cell, the lower and upper Davydov components can each exhibit J-like or H-like behavior, resulting in JJ, JH, and HH components in order of increasing energy, all with unique vibronic signatures. Under certain conditions, null points can exist in either band, leading to a monomer-like absorption spectrum for the corresponding Davydov component. In crystals with four symmetrically equivalent molecules per unit cell, the J- or H-nature of the three orthogonally polarized Davydov components results in four possible combinations, JJJ, JJH, JHH, and HHH in order of increasing energy, all readily identified through vibronic signatures. 

Aims.The scenario of feedback-free starbursts (FFB), which predicts excessively bright galaxies at cosmic dawn as observed using JWST, may provide a natural setting for black hole (BH) growth. This involves the formation of intermediate-mass seed BHs and their runaway mergers into super-massive BHs with high BH-to-stellar mass ratios and low Active Galactic Nucleus (AGN) luminosities. Methods.We present a scenario of merger-driven BH growth in FFB galaxies and study its feasibility. Results.Black hole seeds form within the building blocks of the FFB galaxies, namely, thousands of compact star clusters, each starbursting in a free-fall time of a few million years before the onset of stellar and supernova feedback. The BH seeds form by rapid core collapse in the FFB clusters, in a few free-fall times, which is sped up by the migration of massive stars due to the young, broad stellar mass function and stimulated by a “gravo-gyro” instability due to internal cluster rotation and flattening. BHs of ∼10⁴ M_⊙are expected in ∼10⁶ M_⊙FFB clusters within sub-kiloparsec galactic disks atz​ ∼ ​10. The BHs then migrate to the galaxy center by dynamical friction, hastened by the compact FFB stellar galactic disk configuration. Efficient mergers of the BH seeds will produce ∼10^6 − 8 M_⊙BHs with a BH-to-stellar mass ratio ∼0.01 byz​ ∼ ​4 − 7, as observed. The growth of the central BH by mergers can overcome the bottleneck introduced by gravitational wave recoils if the BHs inspiral within a relatively cold disk or if the escape velocity from the galaxy is boosted by a wet compaction event. Such events, common in massive galaxies at high redshifts, can also help by speeding up the inward BH migration and by providing central gas to assist with the final parsec problem. Conclusions.The cold disk version of the FFB scenario provides a feasible route for the formation of supermassive BHs. 

Abstract Diketopiperazines (DKPs) are chemically and functionally diverse cyclic dipeptides associated primarily with microbes. Few DKPs have been reported from plants and animals; the best characterized is cyclo(His-Pro), found in the mammalian central nervous system, where it arises from the proteolytic cleavage of a thyrotropin-releasing tripeptide hormone. Herein, we report the identification of cyclo(His-Pro) in Arabidopsis (Arabidopsis thaliana), where its levels increase upon abiotic stress conditions, including high salt, heat, and cold. To screen for potential protein targets, we used isothermal shift assays, which examine changes in protein-melting stability upon ligand binding. Among the identified proteins, we focused on the glycolytic enzyme, cytosolic glyceraldehyde-3-phosphate dehydrogenase (GAPC1). Binding between the GAPC1 protein and cyclo(His-Pro) was validated using nano-differential scanning fluorimetry and microscale thermophoresis, and we could further demonstrate that cyclo(His-Pro) inhibits GAPC1 activity with an IC50 of ∼200 μm. This inhibition was conserved in human GAPDH. Inhibition of glyceraldehyde-3-phosphate dehydrogenase activity has previously been reported to reroute carbon from glycolysis toward the pentose phosphate pathway. Accordingly, cyclo(His-Pro) supplementation augmented NADPH levels, increasing the NADPH/NADP+ ratio. Phenotypic screening revealed that plants supplemented with cyclo(His-Pro) were more tolerant to high-salt stress, as manifested by higher biomass, which we show is dependent on GAPC1/2. Our work reports the identification and functional characterization of cyclo(His-Pro) as a modulator of glyceraldehyde-3-phosphate dehydrogenase in plants. 

In recent years, the increasing complexity and safety-critical nature of robotic tasks have highlighted the importance of accurate and reliable robot models. This trend has led to a growing belief that, given enough data, traditional physics-based robot models can be replaced by appropriately trained deep networks or their variants. Simultaneously, there has been a renewed interest in physics-based simulation, fueled by the widespread use of simulators to train reinforcement learning algorithms in the sim-to-real paradigm. The primary objective of this review is to present a unified perspective on the process of determining robot models from data, commonly known as system identification or model learning in different subfields. The review aims to illuminate the key challenges encountered and highlight recent advancements in system identification for robotics. Specifically, we focus on recent breakthroughs that leverage the geometry of the identification problem and incorporate physics-based knowledge beyond mere first-principles model parameterizations. Through these efforts, we strive to provide a contemporary outlook on this problem, bridging classical findings with the latest progress in the field.