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Abstract Bitterness is an important physiological function in the defense responses to avoid toxic foods. The taste receptor 2 family is well known to mediate bitter taste perception in Type II taste cells. Here, we report that the polycystic kidney disease 2-like 1 (PKD2L1) channel is a novel sensor for the bitter aftertaste in Type III taste cells. The PKD2L1 channel showed rebound activation after the washout of quinine, a bitter tastant, in electrophysiological whole-cell recordings of the PKD2L1-expressing HEK293T cells and Ca2+-imaging analysis of Type III taste cells isolated from wild-type PKD2L1 mice. In the short-term two-bottle preference and lick tests in vivo, the wild-type mice avoided normal water while the PKD2L1-knockout mice preferred normal water after they ingested the quinine-containing water. These results may explain the new mechanism of the quinine-triggered bitter aftertaste perception in Type III taste cells.

Mechanical stimuli, such as stretch and resistance training, are essential in regulating the growth and functioning of skeletal muscles. However, the molecular mechanisms involved in sensing mechanical stress during muscle formation remain unclear. Here, we investigated the role of the mechanosensitive ion channel Piezo1 during myogenic progression of both fast and slow muscle satellite cells. We found that Piezo1 level increases during myogenic differentiation and direct manipulation of Piezo1 in muscle stem cells alters the myogenic progression. Indeed, Piezo1 knockdown suppresses myoblast fusion, leading to smaller myotubes. Such an event is accompanied by significant downregulation of the fusogenic protein Myomaker. In parallel, while Piezo1 knockdown also lowers Ca2+ influx in response to stretch, Piezo1 activation increases Ca2+ influx in response to stretch and enhances myoblasts fusion. These findings may help understand molecular defects present in some muscle diseases. Our study shows that Piezo1 is essential for terminal muscle differentiation acting on myoblast fusion, suggesting that Piezo1 deregulation may have implications in muscle aging and degenerative diseases, including muscular dystrophies and neuromuscular disorders.

Aim: The hemodynamic response to mouse systemic anaphylaxis is characterized by an initial hypertension followed by sustained hypotension. However, the defense mechanisms of the sympathetic nervous system against this circulatory disturbance is not known. Here, we investigated the renal sympathetic nerve activity (RSNA) response to mouse systemic anaphylaxis, along with the roles of carotid sinus baroreceptor, vagal nerves and the transient receptor potential vanilloid type 1 channel (TRPV1).Methods: Male ovalbumin-sensitized C57BL/6N mice were used under pentobarbital anesthesia. RSNA, systemic arterial pressure (SAP) and heart rate (HR) were continuously measured for 60 min after the antigen injection.Results: Within 3 min after antigen injection, RSNA decreased along with a transient increase in SAP. Thereafter, RSNA showed a progressive increase during sustained hypotension. In contrast, HR continuously increased. Sinoaortic denervation, but not vagotomy, significantly attenuated the renal sympathoexcitation and tachycardia from 30 and 46 min, respectively, after antigen. The responses of RSNA, SAP and HR to anaphylaxis were not affected by pretreatment with a TRPV1 inhibitor, capsazepine, or by genetic knockout of TRPV1.Conclusion: The mouse systemic anaphylaxis causes a biphasic RSNA response with an initial baroreflex-independent decrease and secondary increase. The antigen-induced sympathoexcitation and tachycardia at the late stage are partly mediated by carotid sinus baroreceptors. Either vagal nerve or TRPV1 does not play any significant roles in the RSNA and HR responses in anesthetized mice.

We present a domain decomposition technique combining the finite-element analysis and a multiscale simulation scheme that is termed the seamless-domain method. This technique is applicable to any type of linear problems and has the below different features from conventional substructuring techniques used for finite-element methods such as the super-elements. Adjacent substructures do not need to have the same finite-element mesh or the same node layout at their interface. Therefore, the proposed technique allows us to connect a substructure having a coarse mesh and another substructure having a fine mesh. Additionally, the neighboring substructures are partially overlapped each other around their interfacial region. The overlapped region attempts to generate continuous dependent-variable distribution(s) at the interfacial region. We present four types of numerical experiments related to linear elasticity to investigate practical feasibility of the proposed technique and evaluate an effect of different finite-element meshes in region shared by two substructures on the computational accuracy.

Carbon fiber reinforced polymers (CFRPs) have high specific strength and many other advantages in mechanical properties compared with conventional metal materials. However, a small out-of-plane impact load can easily cause serious damage in a CFRP laminate because of its laminated structure composed of anisotropic layers. Although ultrasonic inspection is generally performed to detect the damage and estimate its location and size, the method usually requires both long inspection time and a large cost. Thus, a low-cost and in-situ system for monitoring collisions of foreign matters is required to identify the area where the ultrasonic inspection must be conducted. When a foreign matter, which is regarded as a charged body because any object is charged to a greater or lesser extent, approaches and hits grounded electric conductive materials such as a CFRP laminate, an electric current caused by electrostatic induction flows into the ground. We analyzed the electric current and conducted a falling-weight impact test to elucidate the mechanism of generation of the electric current. In addition, we proposed a collision monitoring system which utilizes the characteristic waveform of the electric current and the electrical anisotropy of a CFRP laminate, and conducted a falling-weight impact test to verify the validity of the proposed method. As a result, we succeeded in localizing the collision of the charged body in sufficiently high spatial resolution using the proposed system.

In this paper, we applied a multiscale numerical scheme called the seamless-domain method (SDM) to nonlinear elliptic boundary value problems. Although the SDM is meshfree, it can obtain a high-resolution solution whose dependent-variable gradient(s) is sufficiently smooth and continuous. The SDM models with only coarse-grained points can produce accurate solutions for both linear heat conduction problems and linear elastic problems. This manuscript presents a simple nonlinear solver for the SDM analysis of heterogeneous materials. Although the solver can easily approximate the solutions to nonlinear multiscale problems, it does not require an iterative multiscale analysis at every convergence calculation. In other words, the proposed scheme does not completely interactively couple the multiple scales. We present numerical examples of nonlinear stationary heat conduction analyses of heterogeneous fields and compare the SDM model, the direct finite-element model, and the homogenized model based on the homogenization theory. For a real heterogeneous structure (graphite fiber composite) that did not have strong material nonlinearities, the SDM model using only 925 points gave a solution with similar precisions as an ordinary finite element solution using hundreds of thousands of nodes. To investigate the limitations of the method, we also applied the SDM to imaginary materials with various strengths of thermal property nonlinearities.

This paper uses classical laminate theory (CLT) and experimental methods to predict the longitudinal specific modulus of braided high modulus polyethylene (HMPE) rope without a matrix. When applying conventional CLT, the modulus, braided angle of strand, and packing factor (PF), i.e., the cross-sectional area ratio of the strand to the rope, are required. Because the void (space between strands) and PF of braided rope without a matrix readily change during the application of load, and given the difficulty measuring PF experimentally, it is difficult to predict the modulus by conventional CLT. This paper proposes the use of the unit of N/tex in place of conventional MPa for CLT. This study demonstrates that changes in PF due to void changes can be neglected when using the N/tex unit. The predicted longitudinal specific modulus of the rope using N/tex unit was found to be in qualitatively agreement with the longitudinal modulus measured experimentally.

For real-time load monitoring, we present a new smart lighting protection skin using resistive touchpad techniques that covers measuring objects with a flexible sheet composed of multiple tiny sensors. We measured loading from off-plate direction, including quasi-static indentation and dynamic impact. We believe our method is suitable for load monitoring of composite aircraft structures. A metal film or mesh coving the fiber composite components of our system acts as both the load sensor and wiring, and a lightning protection shield (LPS). The sheet consists of an upper LPS layer and a lower layer, with multiple pressure-sensitive elastomer pills arranged between layers. The lower layer is a grid consisting of high-electrical-resistance nichrome wires and low-resistance copper wires. The pressure-sensitive pill becomes conductive when compressed. When the sensor sheet is indented, a compressed pill creates a new electrical path between the two layers and the electrical potential equalizes at that point. This event triggers the application of a potential across the nichrome wires that form the x axis, enabling measurement of the x coordinate. The orthogonal potential gradient is then applied to the lower layer so that the y coordinate can be measured. The x and y coordinates are recorded quickly and describe the quasi-static load point with an error of 29 mm or less. Additionally, we can estimate the peak value of the impact load by measuring the electrical resistance of the pressure-sensitive pill with an error of 17 %.

The stress intensity factor can be applied as an evaluation parameter of crack growth under small-scale yielding conditions. Moreover, the stress intensity factor corrected by the plastic zone correction can potentially be used as an evaluation parameter of crack growth for small-scale yielding criteria or beyond these criteria. In the previous study, the plastic zone correction method for that purpose was proposed. The method focuses on the gradient of the stress intensity factor at the crack tip, incorporating the term into the correction formula. To investigate the applicability of the correction experimentally, fatigue crack propagation tests were conducted in this study using three types of specimens with different gradients. The results show that the crack growth rate increased when the gradient was large although the effective stress intensity factor range was the same. This indicates that the gradient of the stress intensity factor at the crack tip affects the stress state in the vicinity of the crack tip and the crack growth rate increases as the gradient increases. When the correction of the stress intensity factor was applied, the crack growth rate could be evaluated independently from the gradient of the stress intensity factor. The correction is applicable around small-scale yielding criteria or beyond these criteria, but is not applicable under sufficiently large-scale yielding conditions.

In recent years, thermoplastic CFRP attracts considerable attention especially in aviation and automobile industries due to weldability of thermoplastic CFRP. Ultrasonic testing (UT) is commonly adopted as a testing method for inspecting weld parts although time cost on UT is thought to be problematic. Since eddy current testing (ET) is used for rapid inspection on electrically conductive materials, this paper presents an eddy current based approach for detecting defects in thermoplastic CFRP welded zones. However, it is difficult for conventional ET to detect delamination which is parallel to eddy current although delamination is one of the common forms of weld defect. To detect delamination in thermoplastic CFRP welded zones, new eddy current based approach which utilizes temperature characteristic of electrical conductivity is proposed. The proposal consists of two steps. Firstly, temperature difference between intact zones and defective zones is caused by heating the one side of the weld part. Secondly, the temperature difference is detected by ET utilizing temperature dependency of electrical conductivity.

The stratum corneum (SC), the outermost epidermal layer, consists of nonviable anuclear keratinocytes, called corneocytes, which function as a protective barrier. The exact modes of cell death executed by keratinocytes of the upper stratum granulosum (SG1 cells) remain largely unknown. Here, using intravital imaging combined with intracellular Ca2+- and pH-responsive fluorescent probes, we aimed to dissect the SG1 death process in vivo. We found that SG1 cell death was preceded by prolonged (~60 min) Ca2+ elevation and rapid induction of intracellular acidification. Once such intracellular ionic changes were initiated, they became sustained, irreversibly committing the SG1 cells to corneocyte conversion. Time-lapse imaging of isolated murine SG1 cells revealed that intracellular acidification was essential for the degradation of keratohyalin granules and nuclear DNA, phenomena specific to SC corneocyte formation. Furthermore, intravital imaging showed that the number of SG1 cells exhibiting Ca2+ elevation and the timing of intracellular acidification were both tightly regulated by the transient receptor potential cation channel V3. The functional activity of this protein was confirmed in isolated SG1 cells using whole-cell patch-clamp analysis. These findings provide a theoretical framework for improved understanding of the unique molecular mechanisms underlying keratinocyte-specific death mode, namely corneoptosis. [ABSTRACT FROM AUTHOR]

In this study, changes in b-values with several fracture modes (matrix cracking, de-bonding and fiber breakage) of FRPs were investigated. When AE sources contain single fracture mode, b-value does not change by propagation length. On the other hand, when AE sources contain several fracture modes, b-value changes with propagation length. The change in b-value for multiple fracture modes may occur by change in the proportion of each frequency components after the propagation due to frequency dependence of the attenuation. [ABSTRACT FROM AUTHOR]

Transient receptor potential vanilloid 4 (TRPV4), a calcium-permeable channel, is highly expressed in the apical membrane of choroid plexus epithelial cells (CPECs) in the brain. The function of TRPV4 is unknown. Here, we show physical and functional interaction between TRPV4 and anoctamin 1 (ANO1) in HEK293T cells and CPECs. Chloride currents induced by a TRPV4 activator (GSK1016790A) were markedly increased in an extracellular calcium-dependent manner in HEK293T cells expressing TRPV4 with ANO1, but not with ANO4, ANO6, or ANO10, the mRNAs of which were expressed in the choroid plexus. We also found physical interaction between TRPV4 and ANO1 in both HEK293T cells and choroid plexus. We observed that ANO1 was activated at a warm temperature (37°C) in HEK293T cells and that the heat-evoked chloride currents were markedly enhanced after GSK1016790A application in CPECs. Simultaneous stimulation by warmth and hyposmosis induced chloride current activation in wild-type, but not in TRPV4-deficient, CPECs. Cell volume changes were induced by ANO 1-mediated chloride currents in parallel with membrane potential changes, and the cell volume was significantly decreased at negative membrane potentials by TRPV4-induced ANO1 activation. Thus, physical and functional interactions between TRPV4 and ANO1 can modulate water transport in die choroid plexus. [ABSTRACT FROM AUTHOR]

The urothelium is a sensory structure that contributes to mechanosensation in the urinary bladder. Here, we provide evidence for a critical role for the Piezo1 channel, a newly identified mechanosensory molecule, in the mouse bladder urothelium. We performed a systematic analysis of the molecular and functional expression of Piezo1 channels in the urothelium. Immunofluorescence examination demonstrated abundant expression of Piezo1 in the mouse and human urothelium. Urothelial cells isolated from mice exhibited a Piezo1-dependent increase in cytosolic Ca2+ concentrations in response to mechanical stretch stimuli, leading to potent ATP release; this response was suppressed in Piezo1-knockdown cells. In addition, Piezo1 and TRPV4 distinguished different intensities of mechanical stimulus. Moreover, GsMTx4, an inhibitor of stretch-activated channels, attenuated the Ca2+ influx into urothelial cells and decreased ATP release from them upon stretch stimulation. These results suggest that Piezo1 senses extension of the bladder urothelium, leading to production of an ATP signal. Thus, inhibition of Piezo1 might provide a promising means of treating bladder dysfunction. [ABSTRACT FROM AUTHOR]