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Frailty markers comprise blood metabolites involved in antioxidation, cognition, and mobility
Get PDFAs human society ages globally, age-related disorders are becoming increasingly common. Due to decreasing physiological reserves and increasing organ system dysfunction associated with age, frailty affects many elderly people, compromising their ability to cope with acute stressors. Frail elderly people commonly manifest complex clinical symptoms, including cognitive dysfunction, hypomobility, and impaired daily activity, the metabolic basis of which remains poorly understood. We applied untargeted, comprehensive LC-MS metabolomic analysis to human blood from 19 frail and nonfrail elderly patients who were clinically evaluated using the Edmonton Frail Scale, the MoCA-J for cognition, and the TUG for mobility. Among 131 metabolites assayed, we identified 22 markers for frailty, cognition, and hypomobility, most of which were abundant in blood. Frailty markers included 5 of 6 markers specifically related to cognition and 6 of 12 markers associated with hypomobility. These overlapping sets of markers included metabolites related to antioxidation, muscle or nitrogen metabolism, and amino acids, most of which are decreased in frail elderly people. Five frailty-related metabolites that decreased-1,5-anhydroglucitol, acetyl-carnosine, ophthalmic acid, leucine, and isoleucine-have been previously reported as markers of aging, providing a metabolic link between human aging and frailty. Our findings clearly indicate that metabolite profiles efficiently distinguish frailty from nonfrailty. Importantly, the antioxidant ergothioneine, which decreases in frailty, is neuroprotective. Oxidative stress resulting from diminished antioxidant levels could be a key vulnerability for the pathogenesis of frailty, exacerbating illnesses related to human aging.journal articl
A biologically constrained spiking neural network model of the primate basal ganglia with overlapping pathways exhibits action selection
Get PDFAction selection has been hypothesized to be a key function of the basal ganglia, yet the nuclei involved, their interactions and the importance of the direct/indirect pathway segregation in such process remain debated. Here, we design a spiking computational model of the monkey basal ganglia derived from a previously published population model, initially parameterized to reproduce electrophysiological activity at rest and to embody as much quantitative anatomical data as possible. As a particular feature, both models exhibit the strong overlap between the direct and indirect pathways that has been documented in non-human primates. Here, we first show how the translation from a population to an individual neuron model was achieved, with the addition of a minimal number of parameters. We then show that our model performs action selection, even though it was built without any assumption on the activity carried out during behaviour. We investigate the mechanisms of this selection through circuit disruptions and found an instrumental role of the off-centre/on-surround structure of the MSN-STN-GPi circuit, as well as of the MSN-MSN and FSI-MSN projections. This validates their potency in enabling selection. We finally study the pervasive centromedian and parafascicular thalamic inputs that reach all basal ganglia nuclei and whose influence is therefore difficult to anticipate. Our model predicts that these inputs modulate the responsiveness of action selection, making them a candidate for the regulation of the speed-accuracy trade-off during decision-making.journal articl
Turbulence in a network of rigid fibers
Get PDFThe effect of a network of fixed rigid fibers on fluid flow is investigated by means of three-dimensional direct numerical simulations using an immersed boundary method for the fluid-structure coupling. Different flows are considered (i.e., cellular, parallel, and homogeneous isotropic turbulent flow) to identify the modification of the classic energy budget occurring within canopies or fibrous media, as well as particle-laden flows. First, we investigate the stabilizing effect of the network on the Arnold-Beltrami-Childress cellular flow, showing that, the steady configuration obtained for a sufficiently large fiber concentration mimics the single-phase stable solution at a lower Reynolds number. Focusing on the large-scale dynamics, the effect of the drag exerted by the network on the flow can be effectively modeled by means of a Darcy's friction term. For the latter, we propose a phenomenological expression that is corroborated when extending our analysis to the Kolmogorov parallel flow and homogeneous isotropic turbulence. Furthermore, we examine the overall energy distribution across the various scales of motion, highlighting the presence of small-scale activity with a peak in the energy spectra occurring at the wave number corresponding to the network spacing.journal articl
The Feeling Is Mutual: Clarity of Haptics-Mediated Social Perception Is Not Associated With the Recognition of the Other, Only With Recognition of Each Other
Get PDFThe enactive theory of perception hypothesizes that perceptual access to objects depends on the mastery of sensorimotor contingencies, that is, on the know-how of the regular ways in which changes in sensations depend on changes in movements. This hypothesis can be extended into the social domain: perception of other minds is constituted by mastery of self-other contingencies, that is, by the know-how of the regular ways in which changes in others’ movements depend on changes in one’s movements. We investigated this proposal using the perceptual crossing paradigm, in which pairs of players are required to locate each other in an invisible one-dimensional virtual space by using a minimal haptic interface.We recorded and analyzed the real-time embodied social interaction of 10 pairs of adult participants. The results reveal a process of implicit perceptual learning: on average, clarity of perceiving the other’s presence increased over trials and then stabilized. However, a clearer perception of the other was not associated with correctness of recognition as such, but with both players correctly recognizing each other. Furthermore, the moments of correct mutual recognition tended to happen within seconds. The fact that changes in social experience can only be explained by the successful performance at the level of the dyad, and that this veridical mutual perception tends toward synchronization, lead us to hypothesize that integration of neural activity across both players played a role.journal articl
Ocean currents promote rare species diversity in protists
Get PDFOceans host communities of plankton composed of relatively few abundant species and many rare species. The number of rare protist species in these communities, as estimated in metagenomic studies, decays as a steep power law of their abundance. The ecological factors at the origin of this pattern remain elusive. We propose that chaotic advection by oceanic currents affects biodiversity patterns of rare species. To test this hypothesis, we introduce a spatially explicit coalescence model that reconstructs the species diversity of a sample of water. Our model predicts, in the presence of chaotic advection, a steeper power law decay of the species abundance distribution and a steeper increase of the number of observed species with sample size. A comparison of metagenomic studies of planktonic protist communities in oceans and in lakes quantitatively confirms our prediction. Our results support that oceanic currents positively affect the diversity of rare aquatic microbes.journal articl
Triboluminescence of a new family of CuI–NHC complexes in crystalline solid and in amorphous polymer films
Get PDFTriboluminescent compounds that generate emission of light in response to mechanical stimulus are promising targets in the development of “smart materials” and damage sensors. Among triboluminescent metal complexes, rare-earth europium and terbium complexes are most widely used, while there is no systematic data on more readily available and inexpensive Cu complexes. We report a new family of photoluminescent Cu–NHC complexes that show bright triboluminescence (TL) in the crystal state visible in ambient indoor light under air. Moreover, when these complexes are blended into amorphous polymer films even at small concentrations, TL is easily observed. Observation of TL in polymer films overcomes the limitation of using crystals and opens up possibilities for the development of mechanoresponsive coatings and materials based on inexpensive metals such as Cu. Our results may also have implications for the understanding of the TL effect's origin in polymer films.journal articl
Non-enzymatic and highly sensitive lactose detection utilizing graphene field-effect transistors
Get PDFField-effect transistor (FET) biosensors based on low-dimensional materials are capable of highly sensitive and specific label-free detection of various analytes. In this work, a FET biosensor based on graphene decorated with gold nanoparticles (Au NPs) was fabricated for lactose detection in a liquid-gate measurement configuration. This graphene device is functionalized with a carbohydrate recognition domain (CRD) of the human galectin-3 (hGal-3) protein to detect the presence of lactose from the donor effect of lectin – glycan affinity binding on the graphene. Although the detection of lactose is important because of its ubiquitous presence in food and for disease related applications (lactose intolerance condition), in this work we exploit the lectin/carbohydrate interaction to develop a device that in principle could specifically detect very low concentrations of any carbohydrate. The biosensor achieved an effective response to lactose concentrations over a dynamic range from 1 fM to 1 pM (10−15 to 10−12 mol L−1) with a detection limit of 200 aM, a significant enhancement over previous electrochemical graphene devices. The FET sensor response is also specific to lactose at aM concentrations, indicating the potential of a combined lectin and graphene FET (G-FET) sensor to detect carbohydrates at high sensitivity and specificity for disease diagnosis.journal articl
Proton-responsive naphthyridinone-based RuII complexes and their reactivity with water and alcohols
Get PDFWe report the synthesis and reactivity of RuII complexes with a new naphthyridinone-substituted phosphine ligand, 7-(diisopropylphosphinomethyl)-1,8-naphthyridin-2(1H)-one (L-H), which contains two reactive sites that can potentially be deprotonated by a strong base: an NH proton of naphthyridinone and a methylene arm attached to the phosphine. In the absence of a base, the stable bis-ligated complex Ru(L-H)2Cl2 (1) containing two NH groups in the secondary coordination sphere is formed. Upon further reaction with a base, a doubly deprotonated, dimeric complex is obtained, [Ru2(L*-H)2(L)2] (2), in which two of the four ligands undergo deprotonation at the NH (L), while the other two ligands are deprotonated at the methylene groups (L*-H) as confirmed by an X-ray diffraction study; intramolecular hydrogen bonding is present between the NH group of one ligand and an O-atom of another ligand in the dimeric structure, which stabilizes the observed geometry of the complex. Complex 2 reacts with protic solvents such as water or methanol generating aqua Ru(L)2(OH2)2 (3) or methanol complexes Ru(L)2(MeOH)2 (4), respectively, both exhibiting intramolecular H-bonded patterns with surrounding ligands at least in the solid state. These complexes react with benzyl alcohols to give aldehydes via base-free acceptorless dehydrogenation.journal articl
Investigation of the Sense of Agency in Social Cognition, Based on Frameworks of Predictive Coding and Active Inference: A Simulation Study on Multimodal Imitative Interaction
Get PDFWhen agents interact socially with different intentions (or wills), conflicts are difficult to avoid. Although the means by which social agents can resolve such problems autonomously has not been determined, dynamic characteristics of agency may shed light on underlying mechanisms. Therefore, the current study focused on the sense of agency, a specific aspect of agency referring to congruence between the agent's intention in acting and the outcome, especially in social interaction contexts. Employing predictive coding and active inference as theoretical frameworks of perception and action generation, we hypothesize that regulation of complexity in the evidence lower bound of an agent's model should affect the strength of the agent's sense of agency and should have a significant impact on social interactions. To evaluate this hypothesis, we built a computational model of imitative interaction between a robot and a human via visuo-proprioceptive sensation with a variational Bayes recurrent neural network, and simulated the model in the form of pseudo-imitative interaction using recorded human body movement data, which serve as the counterpart in the interactions. A key feature of the model is that the complexity of each modality can be regulated differently by changing the values of a hyperparameter assigned to each local module of the model. We first searched for an optimal setting of hyperparameters that endow the model with appropriate coordination of multimodal sensation. These searches revealed that complexity of the vision module should be more tightly regulated than that of the proprioception module because of greater uncertainty in visual information flow. Using this optimally trained model as a default model, we investigated how changing the tightness of complexity regulation in the entire network after training affects the strength of the sense of agency during imitative interactions. The results showed that with looser regulation of complexity, an agent tends to act more egocentrically, without adapting to the other. In contrast, with tighter regulation, the agent tends to follow the other by adjusting its intention. We conclude that the tightness of complexity regulation significantly affects the strength of the sense of agency and the dynamics of interactions between agents in social settings.journal articl
CsPbBrxI3-x thin films with multiple ammonium ligands for low turn-on pure-red perovskite light-emitting diodes
Get PDFAll-inorganic α-CsPbBrxI3-x perovskites featuring nano-sized crystallites show great potential for pure-red light-emitting diode (LED) applications. Currently, the CsPbBrxI3–x LEDs based on nano-sized α-CsPbBrxI3-x crystallites have been fabricated mainly via the classical colloidal route including a tedious procedure of nanocrystal synthesis, purification, ligand or anion exchange, film casting, etc. With the usually adopted conventional LED device structure, only high turn-on voltages (> 2.7) have been achieved for CsPbBrxI3-x LEDs. Moreover, this mix-halide system may suffer from severe spectra-shift under bias. In this report, CsPbBrxI3-x thin films featuring nano-sized crystallites are prepared by incorporating multiple ammonium ligands in a one-step spin-coating route. The multiple ammonium ligands constrain the growth of CsPbBrxI3-x nanograins. Such CsPbBrxI3-x thin films benefit from quantum confinement. The corresponding CsPbBrxI3-x LEDs, adopting a conventional LED structure of indium-doped tin oxide (ITO)/poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS)/CsPbBrxI3-x/[6, 6]-phenyl C61 butyric acid methyl ester (PCBM)/bathocuproine (BCP)/Al, emit pure-red color at Commission Internationale de l’éclairage (CIE) coordinates of (0.709, 0.290), (0.711, 0.289), etc., which represent the highest color-purity for reported pure-red perovskite LEDs and meet the Rec. 2020 requirement at CIE (0.708, 0.292) very well. The CsPbBrxI3-x LED shows a low turn-on voltage of 1.6 V, maximum external quantum efficiency of 8.94%, high luminance of 2,859 cdm−2, and good color stability under bias.journal articl