Artificial molecular machines are able to produce and exploit precise nanoscale actuations in response to chemical or physical triggers. Recent scientific efforts have been devoted to the ...integration, orientation, and interfacing of large assemblies of molecular machines in order to harness their collective actuations at larger length scale and up to the generation of macroscopic motions. Making use of such “hierarchical mechanics” represents a fundamentally new approach for the conception of stimuli‐responsive materials. Furthermore, because some molecular machines can function as molecular motors—which are capable of cycling a unidirectional motion out of thermodynamic equilibrium and progressively increasing the work delivered to their environment—one can expect unique opportunities to design new kinds of mechanically active materials and devices capable of autonomous behavior when supplied by an external source of energy. Recently reported achievements are summarized, including the integration of molecular machines at surfaces and interfaces, in 3D self‐assembled materials, as well as in liquid crystals and polymer materials. Their detailed functioning principles as well as their functional properties are discussed along with their potential applications in various domains such as sensing, drug delivery, electronics, optics, plasmonics, and mechanics.
New types of 2D and 3D stimuli‐responsive materials can be constructed by integrating molecular machines as part of their building blocks. The transfer of mechanical actuations from the nanometric scale to the macroscopic one can be supported by several transmission processes and offers a potential pathway to active functional materials for applications in medicine, information technologies, and robotics.
mTORC1 promotes cell growth in response to nutrients and growth factors. Insulin activates mTORC1 through the PI3K-Akt pathway, which inhibits the TSC1-TSC2-TBC1D7 complex (the TSC complex) to turn ...on Rheb, an essential activator of mTORC1. However, the mechanistic basis of how this pathway integrates with nutrient-sensing pathways is unknown. We demonstrate that insulin stimulates acute dissociation of the TSC complex from the lysosomal surface, where subpopulations of Rheb and mTORC1 reside. The TSC complex associates with the lysosome in a Rheb-dependent manner, and its dissociation in response to insulin requires Akt-mediated TSC2 phosphorylation. Loss of the PTEN tumor suppressor results in constitutive activation of mTORC1 through the Akt-dependent dissociation of the TSC complex from the lysosome. These findings provide a unifying mechanism by which independent pathways affecting the spatial recruitment of mTORC1 and the TSC complex to Rheb at the lysosomal surface serve to integrate diverse growth signals.
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•Insulin triggers acute dissociation of the TSC complex from Rheb at the lysosome•Release of the TSC complex from the lysosome is required to activate mTORC1•Dissociation of TSC complex from the lysosome requires Akt phosphorylation of TSC2•The TSC complex is constitutively dissociated from the lysosome in PTEN null cells
Activation of the PI3K-Akt pathway signals to mTORC1 by stimulating release of the TSC complex from Rheb at the lysosomal surface, where mTORC1 is independently recruited through amino acid sensing mechanisms. This spatial regulation provides a mechanism to integrate growth signals upstream of mTORC1.
Organisms make two types of decisions on a regular basis. Perceptual decisions are determined by objective states of the world (e.g., melons are bigger than apples), whereas value-based decisions are ...determined by subjective preferences (e.g., I prefer apples to melons). Theoretical accounts suggest that both types of choice involve neural computations accumulating evidence for the choice alternatives; however, little is known about the overlap or differences in the processes underlying perceptual versus value-based decisions. We analyzed EEG recordings during a paradigm where perceptual- and value-based choices were based on identical stimuli. For both types of choice, evidence accumulation was evident in parietal gamma-frequency oscillations, whereas a similar frontal signal was unique for value-based decisions. Fronto-parietal synchronization of these signals predicted value-based choice accuracy. These findings uncover how decisions emerge from topographic- and frequency-specific oscillations that accumulate distinct aspects of evidence, with large-scale synchronization as a mechanism integrating these spatially distributed signals.
•Frequency-specific oscillations encode distinct aspects of evidence during choice•Parietal gamma oscillations support evidence accumulation in valuation and perception•Frontal gamma oscillations support evidence accumulation in valuation•Fronto-parietal gamma coupling relates to the accuracy of value-based decisions
Polania et al. show that similar mechanisms underlie choices based on perceptual information or subjective preferences. These mechanisms integrate choice-relevant (perceptual- or value-based) evidence by frequency-specific parietal and frontal oscillations, which are integrated by large-scale synchronization.
Esophageal squamous cell carcinoma (ESCC) accounts for about 90% of the 456,000 incident esophageal cancers each year. Regions of high incidence include Eastern to Central Asia, along the Rift Valley ...in East Africa, and into South Africa. There are many causes of ESCC, which vary among regions. Early studies in France associated smoking cigarettes and heavy alcohol consumption with high rates of ESCC, but these factors cannot explain the high incidence in other regions. We discuss other risk factors for ESCC, including polycyclic aromatic hydrocarbons from a variety of sources, high-temperature foods, diet, and oral health and the microbiome—all require further research. A growing list of defined genomic regions affects susceptibility, but large genome-wide association studies have been conducted with ethnic Chinese subjects only; more studies are called for in the rest of Asia and Africa. ESCC has been understudied, but growing infrastructure in more high-incidence countries will allow rapid progress in our understanding.
Human altruism shaped our evolutionary history and pervades social and political life. There are, however, enormous individual differences in altruism. Some people are almost completely selfish, ...while others display strong altruism, and the factors behind this heterogeneity are only poorly understood. We examine the neuroanatomical basis of these differences with voxel-based morphometry and show that gray matter (GM) volume in the right temporoparietal junction (TPJ) is strongly associated with both individuals' altruism and the individual-specific conditions under which this brain region is recruited during altruistic decision making. Thus, individual differences in GM volume in TPJ not only translate into individual differences in the general propensity to behave altruistically, but they also create a link between brain structure and brain function by indicating the conditions under which individuals are likely to recruit this region when they face a conflict between altruistic and selfish acts.
► Econometric evidence reveals large individual differences in behavioral altruism ► Gray matter volume in the right TPJ predicts subjects' behavioral altruism ► GM in right TPJ predicts functional activity profile in TPJ during altruistic choice ► Individual differences in altruism relate to both structure and function of right TPJ
Morishima et al. show that gray matter volume in the right temporoparietal junction predicts individuals' altruism and individual-specific conditions under which this brain region is recruited during altruistic decision making, revealing a link between brain structure and functional activity in altruistic choice.
Low, intermediate and high strain rate tensile experiments are carried Out on flat smooth, notched and central-hole tensile specimens extracted from advanced high strength steel sheets. A split ...Hopkinson pressure bar testing system is used in conjunction with a load inversion device to perform the high strain rate tension experiments. Selected surface strains, as well as local displacements, are measured using high speed photography in conjunction with planar digital image correlation (video extensometer). Through thickness necking precedes fracture in all experiments. A hybrid experimental-numerical approach is therefore employed to determine the strain to fracture inside the neck. To obtain an accurate description of the local strain fields at very large deformations, a plasticity model with a Johnson-Cook type of rate and temperature-dependency and a combined Swift-Voce strain hardening law is used in conjunction with a non-associated anisotropic flow rule. The incremental change in temperature is computed using a strain rate dependent weighting function instead of solving the thermal field equations. The comparison of the computed and measured force-displacement curves and surface strain histories shows good agreement before and after the onset of necking. From each experiment, the loading path to fracture is determined describing the evolution of the equivalent plastic strain in terms of the stress triaxiality, Lode angle parameter, strain rate and temperature. An empirical extension of the stress-state dependent Hosford-Coulomb fracture initiation model is proposed to account for the effect of strain rate on the onset of ductile fracture. The model is subsequently calibrated and successfully validated using the results from fracture experiments on DP590 and TRIP780 steels.
Direct recognition of invading pathogens by innate immune cells is a critical driver of the inflammatory response. However, cells of the innate immune system can also sense their local ...microenvironment and respond to physiological fluctuations in temperature, pH, oxygen and nutrient availability, which are altered during inflammation. Although cells of the immune system experience force and pressure throughout their life cycle, little is known about how these mechanical processes regulate the immune response. Here we show that cyclical hydrostatic pressure, similar to that experienced by immune cells in the lung, initiates an inflammatory response via the mechanically activated ion channel PIEZO1. Mice lacking PIEZO1 in innate immune cells showed ablated pulmonary inflammation in the context of bacterial infection or fibrotic autoinflammation. Our results reveal an environmental sensory axis that stimulates innate immune cells to mount an inflammatory response, and demonstrate a physiological role for PIEZO1 and mechanosensation in immunity.
Over the past several decades a large amount of data have established that glial cells, the main cell population in the brain, dynamically interact with neurons and thus impact their activity and ...survival. One typical feature of glia is their marked expression of several connexins, the membrane proteins forming intercellular gap junction channels and hemichannels. Pannexins, which have a tetraspan membrane topology as connexins, are also detected in glial cells. Here, we review the evidence that connexin and pannexin channels are actively involved in dynamic and metabolic neuroglial interactions in physiological as well as in pathological situations. These features of neuroglial interactions open the way to identify novel non-neuronal aspects that allow for a better understanding of behavior and information processing performed by neurons. This will also complement the "neurocentric" view by facilitating the development of glia-targeted therapeutic strategies in brain disease.
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