Simultaneous loss of skeletal muscle myosin heavy chain IIx and IIb causes severe skeletal muscle hypoplasia in postnatal mice.

The skeletal muscle myosin heavy chain (MyHC) is a fundamental component of the sarcomere structure and muscle contraction. Two of the three adult fast MyHCs, MyHC-IIx and MyHC-IIb, are encoded by Myh1 and Myh4, respectively. However, skeletal muscle disorders have not yet been linked to these genes in humans. MyHC-IIb is barely detectable in human skeletal muscles. Thus, to characterize the molecular function of skeletal muscle MyHCs in humans, investigation of the effect of simultaneous loss of MyHC-IIb and other MyHCs on skeletal muscle in mice is essential. Here, we generated double knockout (dKO) mice with simultaneous loss of adult fast MyHCs by introducing nonsense frameshift mutations into the Myh1 and Myh4 genes. The dKO mice appeared normal after birth and until 2 weeks of age but showed severe skeletal muscle hypoplasia after 2 weeks. In 3-week-old dKO mice, increased expression of other skeletal muscle MyHCs, such as MyHC-I, MyHC-IIa, MyHC-neo, and MyHC-emb, was observed. However, these expressions were not sufficient to compensate for the loss of MyHC-IIb and MyHC-IIx. Moreover, the aberrant sarcomere structure with altered expression of sarcomere components was observed in dKO mice. Our findings imply that the simultaneous loss of MyHC-IIb and MyHC-IIx is substantially detrimental to postnatal skeletal muscle function and will contribute to elucidating the molecular mechanisms of skeletal muscle wasting disorders caused by the loss of skeletal muscle MyHCs.

Talk to us about your skin: The relationship between spoken language and haptic exploratory procedures.

OBJECTIVE: To enhance satisfaction, the cosmetics industry needs to clearly understand consumers' descriptions of their key tactile preferences. It is difficult for researchers to understand verbal descriptions from people whose native language is different from their own. Previous research has implied that some sensory words with the same lexical meanings have been observed in different haptic exploratory procedures (HEPs). Therefore, our study aims to investigate and understand the key tactile perceptions of people from five different countries based on their descriptions and their HEPs. METHODS: In Experiment 1, 1545 participants living in the US, Japan, China, Italy, and Thailand described their major tactile perceptions as efficacy in skincare, and we analysed the frequency of each word used in their answers. In Experiment 2, we confirmed the task to observe HEPs for Chinese, Italian, and Thai participants. A total of 24 participants in China, 33 participants in Italy, and 30 participants in Thailand freely explored their faces with their hands and answered which side more closely matched the major tactile adjectives. Experts classified the observed HEPs into six classifications within two categories and three contact area sizes and investigated the cultural differences. RESULTS: More than 2% of the Chinese, Italian, Thai, US, and Japanese participants described 33, 20, 29, 22, and 18 words, respectively, as efficacy in skincare. Verified words that described the major tactile perceptions in each native language had the same meanings as moistness, firmness, softness, smoothness, and so on. We could confirm the HEPs of these major feelings for the participants from each culture. Chinese and Thai participants' HEPs for moistness or softness were observed with a pressing movement. Conversely, Italian participants' HEPs for moistness or softness were observed with a rubbing movement. CONCLUSION: This study showed that words with the same lexical meanings evoked different HEPs. The results imply that different HEPs can provide different physical stimuli on the skin. Therefore, it is important to survey both objects and HEPs to better understand the tactile experience.

OBJECTIF: Pour améliorer la satisfaction, l'industrie cosmétique doit bien comprendre les descriptions que font les consommateurs de leurs principales préférences tactiles. Il est difficile pour les chercheurs de comprendre les descriptions verbales des personnes dont la langue maternelle est différente de la leur. Des recherches antérieures ont suggéré que certains mots sensoriels ayant les mêmes significations lexicales ont été observés dans différentes procédures exploratoires haptiques (PEH). Par conséquent, notre étude vise à étudier et à comprendre les perceptions tactiles clés des personnes de cinq pays différents en fonction de leurs descriptions et de leurs PEH. MÉTHODES: Dans l'expérience 1 545 participantes vivant aux États­Unis, au Japon, en Chine, en Italie et en Thaïlande ont décrit leurs principales perceptions tactiles comme l'efficacité dans les soins de la peau, et nous avons analysé la fréquence de chaque mot utilisé dans leurs réponses. Dans l'expérience 2, nous l'avons confirmé en observant les PEH pour les participantes chinoises, italiennes et thaïs. 24 participantes en Chine, 33 participantes en Italie et 30 participantes en Thaïlande ont librement exploré leur visage avec leurs mains et ont répondu à la question de savoir quel côté correspondait le mieux aux principaux adjectifs tactiles. Les experts ont classé les PEH observées en six classifications dans deux catégories et trois tailles de surface de contact, et ont étudié les différences culturelles. RÉSULTAT: Plus de deux pour cent des participantes chinoises, italiennes, thaïs, américaines et japonaises ont décrit 33, 20, 29, 22 et 18 mots, respectivement, comme une efficacité dans les soins de la peau. Les mots vérifiés qui décrivaient les principales perceptions tactiles dans chaque langue maternelle ayant les mêmes significations sont l'humidité, la fermeté, la douceur, la texture lisse, etc. Nous avons pu confirmer les PEH de ces sensations majeures pour les participants de chaque culture. Les PEH des participantes chinoises et thaïs pour l'humidité ou la douceur ont été observées avec un mouvement de pression. A l'inverse, les PEH pour l'humidité ou la douceur des participantes italiennes ont été observées avec un mouvement de frottement. CONCLUSION: Cette étude a montré que les mots ayant les mêmes significations lexicales évoquaient différentes PEH. Les résultats impliquent que différentes PEH peuvent fournir différents stimuli physiques sur la peau. Par conséquent, il est important d'étudier les objets et les PEH pour mieux comprendre l'expérience tactile.

Myogenin promoter-associated lncRNA Myoparr is essential for myogenic differentiation.

Promoter-associated long non-coding RNAs (lncRNAs) regulate the expression of adjacent genes; however, precise roles of these lncRNAs in skeletal muscle remain largely unknown. Here, we characterize a promoter-associated lncRNA, Myoparr, in myogenic differentiation and muscle disorders. Myoparr is expressed from the promoter region of the mouse and human myogenin gene, one of the key myogenic transcription factors. We show that Myoparr is essential both for the specification of myoblasts by activating neighboring myogenin expression and for myoblast cell cycle withdrawal by activating myogenic microRNA expression. Mechanistically, Myoparr interacts with Ddx17, a transcriptional coactivator of MyoD, and regulates the association between Ddx17 and the histone acetyltransferase PCAF Myoparr also promotes skeletal muscle atrophy caused by denervation, and knockdown of Myoparr rescues muscle wasting in mice. Our findings demonstrate that Myoparr is a novel key regulator of muscle development and suggest that Myoparr is a potential therapeutic target for neurogenic atrophy in humans.

Comprehensive analysis of elemental distribution in human skin using laser ablation inductively coupled plasma mass spectrometry.

BACKGROUND: Multiple chemical elements play roles in skin homeostasis. The distribution of elements in skin has been studied by X-ray microanalysis methods and fluorescence microscopy using chemical indicators, but the former requires complicated sample preparation steps, while the latter is limited by the availability of suitable chemical indicators. MATERIALS AND METHODS: We applied laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) to measure the distributions of thirty-eight elements in human skin. RESULTS: Among the target elements, nine (calcium: 40 Ca, 44 Ca, zinc: 64 Zn, 66 Zn, phosphorus: 31 P, potassium: 39 K, sodium: 23 Na, sulfur: 34 S, copper: 63 Cu, magnesium: 24 Mg, and iron: 56 Fe) showed distribution patterns that were consistent with previous reports, and four others (iodine: 127 I, barium: 138 Ba, strontium: 88 Sr, and molybdenum: 95 Mo) were detected for the first time in human skin. CONCLUSION: The method described here requires only slicing into sections to prepare a sample for measurement, so the elemental distributions are minimally disturbed, and comprehensive information can be obtained rapidly. The method is expected to be useful for research in a variety of fields, including skin diseases, aging, and allergenicity.

Myoparr-Associated and -Independent Multiple Roles of Heterogeneous Nuclear Ribonucleoprotein K during Skeletal Muscle Cell Differentiation.

RNA-binding proteins (RBPs) regulate cell physiology via the formation of ribonucleic-protein complexes with coding and non-coding RNAs. RBPs have multiple functions in the same cells; however, the precise mechanism through which their pleiotropic functions are determined remains unknown. In this study, we revealed the multiple inhibitory functions of heterogeneous nuclear ribonucleoprotein K (hnRNPK) for myogenic differentiation. We first identified hnRNPK as a lncRNA Myoparr binding protein. Gain- and loss-of-function experiments showed that hnRNPK repressed the expression of myogenin at the transcriptional level. The hnRNPK-binding region of Myoparr was required to repress myogenin expression. Moreover, hnRNPK repressed the expression of a set of genes coding for aminoacyl-tRNA synthetases in a Myoparr-independent manner. Mechanistically, hnRNPK regulated the eIF2α/Atf4 pathway, one branch of the intrinsic pathways of the endoplasmic reticulum sensors, in differentiating myoblasts. Thus, our findings demonstrate that hnRNPK plays lncRNA-associated and -independent multiple roles during myogenic differentiation, indicating that the analysis of lncRNA-binding proteins will be useful for elucidating both the physiological functions of lncRNAs and the multiple functions of RBPs.

An Analysis of Differentially Expressed Coding and Long Non-Coding RNAs in Multiple Models of Skeletal Muscle Atrophy.

The loss of skeletal muscle mass (muscle atrophy or wasting) caused by aging, diseases, and injury decreases quality of life, survival rates, and healthy life expectancy in humans. Although long non-coding RNAs (lncRNAs) have been implicated in skeletal muscle formation and differentiation, their precise roles in muscle atrophy remain unclear. In this study, we used RNA-sequencing (RNA-Seq) to examine changes in the expression of lncRNAs in four muscle atrophy conditions (denervation, casting, fasting, and cancer cachexia) in mice. We successfully identified 33 annotated lncRNAs and 18 novel lncRNAs with common expression changes in all four muscle atrophy conditions. Furthermore, an analysis of lncRNA-mRNA correlations revealed that several lncRNAs affected small molecule biosynthetic processes during muscle atrophy. These results provide novel insights into the lncRNA-mediated regulatory mechanism underlying muscle atrophy and may be useful for the identification of promising therapeutic targets.

Sensory words may facilitate certain haptic exploratory procedures in facial cosmetics.

OBJECTIVE: Many people want to have healthy facial skin. They tend to check their skin's condition by touching their face with their hands. In the cosmetic industry, we need to understand what consumers are perceiving in a tactile sense when touching their own facial skin. The purpose of this study was to investigate these observation methods in order to systematically understand people's haptic exploratory procedures (HEPs). METHODS: Thirty-four participants living in the United States and twenty-two participants living in Japan freely explored their faces and answered which side felt more closely related to the six tactile adjectives. A new analysis was applied to classify the observed HEPs into six classifications within two categories and three sizes of contact area by experts. RESULT: It was confirmed that the new task was useful to observe the HEPs for participants from United States and Japan. The US participants' HEPs for 'moisturized' were mainly a middle-sized contact area using a stroking motion. On the other hand, Japanese participants' HEPs for 'moisturized' ('shittori' in Japanese) mainly used a pushing movement. Moreover, the US participants' HEPs for 'soft' included both pushing and stroking, but Japanese participants HEPs for 'soft' ('yawarakai' in Japanese) were again mainly pushing. CONCLUSION: This study suggests that the proposed analysis method enables the systematic understanding of HEPs when checking the skin, along with the cross-cultural differences affecting those procedures. These systematic findings could allow cosmetic formulators to have a better understanding of the tactile sensations consumers themselves are feeling in a variety of different global markets.

OBJECTIF: de nombreuses personnes veulent avoir une peau du visage en bonne santé. Elles ont tendance à examiner l'état de leur peau en se touchant le visage avec les mains. Dans l'industrie cosmétique, nous devons comprendre ce que les consommateurs perçoivent d'un point de vue tactile lorsqu'ils se touchent la peau du visage. L'objectif de cette étude était d'évaluer ces méthodes d'observation afin de comprendre de manière systématique les procédures exploratoires haptiques (PEH) des individus. MÉTHODES: trente-quatre participants vivant aux États-Unis et vingt-deux vivant au Japon ont librement examiné leur visage en le touchant et indiqué quel côté semblait le plus proche des six adjectifs tactiles. Une nouvelle analyse a été appliquée pour classer les PEH observées en six groupes de classification au sein de deux catégories et trois tailles de zone de contact par des experts. RÉSULTAT: il a été confirmé que cette nouvelle étude était utile pour observer les PEH chez les participants provenant des États-Unis et du Japon. Les PEH des participants américains pour l'adjectif « hydratée ¼ correspondaient principalement à des mouvements de caresse sur une zone de contact de taille moyenne. En revanche, les PEH des participants japonais pour « hydratée ¼ (« shittori ¼ en japonais) correspondaient principalement à des mouvements de pression. De plus, les PEH des participants américains pour l'adjectif « douce ¼ comprenaient à la fois des mouvements de caresse et de pression, mais celles des participants japonais pour « douce ¼ (« yawarakai ¼ en japonais) correspondaient de nouveau principalement à des mouvements de pression. CONCLUSION: cette étude suggère que la méthode d'analyse proposée permet une compréhension systématique des PEH lors de l'examen de la peau, ainsi que des différences interculturelles influençant ces procédures. Ces résultats systématiques pourraient permettre aux formulateurs de cosmétiques de mieux comprendre les sensations tactiles des consommateurs eux-mêmes pour un ensemble de marchés mondiaux différents.

Epidermal Merkel cells are mechanosensory cells that tune mammalian touch receptors.

Touch submodalities, such as flutter and pressure, are mediated by somatosensory afferents whose terminal specializations extract tactile features and encode them as action potential trains with unique activity patterns. Whether non-neuronal cells tune touch receptors through active or passive mechanisms is debated. Terminal specializations are thought to function as passive mechanical filters analogous to the cochlea's basilar membrane, which deconstructs complex sounds into tones that are transduced by mechanosensory hair cells. The model that cutaneous specializations are merely passive has been recently challenged because epidermal cells express sensory ion channels and neurotransmitters; however, direct evidence that epidermal cells excite tactile afferents is lacking. Epidermal Merkel cells display features of sensory receptor cells and make 'synapse-like' contacts with slowly adapting type I (SAI) afferents. These complexes, which encode spatial features such as edges and texture, localize to skin regions with high tactile acuity, including whisker follicles, fingertips and touch domes. Here we show that Merkel cells actively participate in touch reception in mice. Merkel cells display fast, touch-evoked mechanotransduction currents. Optogenetic approaches in intact skin show that Merkel cells are both necessary and sufficient for sustained action-potential firing in tactile afferents. Recordings from touch-dome afferents lacking Merkel cells demonstrate that Merkel cells confer high-frequency responses to dynamic stimuli and enable sustained firing. These data are the first, to our knowledge, to directly demonstrate a functional, excitatory connection between epidermal cells and sensory neurons. Together, these findings indicate that Merkel cells actively tune mechanosensory responses to facilitate high spatio-temporal acuity. Moreover, our results indicate a division of labour in the Merkel cell-neurite complex: Merkel cells signal static stimuli, such as pressure, whereas sensory afferents transduce dynamic stimuli, such as moving gratings. Thus, the Merkel cell-neurite complex is an unique sensory structure composed of two different receptor cell types specialized for distinct elements of discriminative touch.

Expression Levels of Long Non-Coding RNAs Change in Models of Altered Muscle Activity and Muscle Mass.

Skeletal muscle is a highly plastic organ that is necessary for homeostasis and health of the human body. The size of skeletal muscle changes in response to intrinsic and extrinsic stimuli. Although protein-coding RNAs including myostatin, NF-κß, and insulin-like growth factor-1 (IGF-1), have pivotal roles in determining the skeletal muscle mass, the role of long non-coding RNAs (lncRNAs) in the regulation of skeletal muscle mass remains to be elucidated. Here, we performed expression profiling of nine skeletal muscle differentiation-related lncRNAs (DRR, DUM1, linc-MD1, linc-YY1, LncMyod, Neat1, Myoparr, Malat1, and SRA) and three genomic imprinting-related lncRNAs (Gtl2, H19, and IG-DMR) in mouse skeletal muscle. The expression levels of these lncRNAs were examined by quantitative RT-PCR in six skeletal muscle atrophy models (denervation, casting, tail suspension, dexamethasone-administration, cancer cachexia, and fasting) and two skeletal muscle hypertrophy models (mechanical overload and deficiency of the myostatin gene). Cluster analyses of these lncRNA expression levels were successfully used to categorize the muscle atrophy models into two sub-groups. In addition, the expression of Gtl2, IG-DMR, and DUM1 was altered along with changes in the skeletal muscle size. The overview of the expression levels of lncRNAs in multiple muscle atrophy and hypertrophy models provides a novel insight into the role of lncRNAs in determining the skeletal muscle mass.

Promethazine Hydrochloride Inhibits Ectopic Fat Cell Formation in Skeletal Muscle.

Fatty degeneration of skeletal muscle leads to muscle weakness and loss of function. Preventing fatty degeneration in skeletal muscle is important, but no drug has been used clinically. In this study, we performed drug repositioning using human platelet-derived growth factor receptor α (PDGFRα)-positive mesenchymal progenitors that have been proved to be an origin of ectopic adipocytes in skeletal muscle. We found that promethazine hydrochloride (PH) inhibits adipogenesis in a dose-dependent manner without cell toxicity. PH inhibited expression of adipogenic markers and also suppressed phosphorylation of cAMP response-element binding protein, which was reported to be a primary regulator of adipogenesis. We established a mouse model of tendon rupture with intramuscular fat deposition and confirmed that emerged ectopic adipocytes are derived from PDGFRα+ cells using lineage tracing mice. When these injured mice were treated with PH, formation of ectopic adipocytes was suppressed significantly. Our results show that PH inhibits PDGFRα+ mesenchymal progenitor-dependent ectopic adipogenesis in skeletal muscle and suggest that treatment with PH can be a promising approach to prevent fatty degeneration of skeletal muscle.

Distinctive molecular responses to ultraviolet radiation between keratinocytes and melanocytes.

Solar ultraviolet radiation (UVR) is the major risk factor for skin carcinogenesis. To gain new insights into the molecular pathways mediating UVR effects in the skin, we performed comprehensive transcriptomic analyses to identify shared and distinctive molecular responses to UVR between human keratinocytes and melanocytes. Keratinocytes and melanocytes were irradiated with varying doses of UVB (10, 20 and 30 mJ/cm(2) ) then analysed by RNA-Seq at different time points post-UVB radiation (4, 24 and 72 h). Under basal conditions, keratinocytes and melanocytes expressed similar number of genes, although they each expressed a distinctive subset of genes pertaining to their specific cellular identity. Upon UVB radiation, keratinocytes displayed a clear pattern of time- and dose-dependent changes in gene expression that was different from melanocytes. The early UVB-responsive gene set (4 h post-UVR) differed significantly from delayed UVB-responsive gene sets (24 and 72 h). We also identified multiple novel UVB signature genes including PRSS23, SERPINH1, LCE3D and CNFN, which were conserved between melanocyte and keratinocyte lines from different individuals. Taken together, our findings elucidated both common and distinctive molecular features between melanocytes and keratinocytes and uncovered novel UVB signature genes that might be utilized to predict UVB photobiological effects on the skin.

Mechanotransduction in epidermal Merkel cells.

The cellular and molecular basis of vertebrate touch reception remains least understood among the traditional five senses. Somatosensory afferents that innervate the skin encode distinct tactile qualities, such as flutter, slip, and pressure. Gentle touch is thought to be transduced by somatosensory afferents whose tactile end organs selectively filter mechanical stimuli. These tactile end organs comprise afferent terminals in association with non-neuronal cell types such as Merkel cells, keratinocytes, and Schwann cells. An open question is whether these non-neuronal cells serve primarily as passive mechanical filters or whether they actively participate in mechanosensory transduction. This question has been most extensively studied in Merkel cells, which are epidermal cells that complex with sensory afferents in regions of high tactile acuity such as fingertips, whisker follicles, and touch domes. Merkel cell-neurite complexes mediate slowly adapting type I (SAI) responses, which encode sustained pressure and represent object features with high fidelity. How Merkel cells contribute to unique SAI firing patterns has been debated for decades; however, three recent studies in rodent models provide some direct answers. First, whole-cell recordings demonstrate that Merkel cells are touch-sensitive cells with fast, mechanically activated currents that require Piezo2. Second, optogenetics and intact recordings show that Merkel cells mediate sustained SAI firing. Finally, loss-of-function studies in transgenic mouse models reveal that SAI afferents are also touch sensitive. Together, these studies identify molecular mechanisms of mechanotransduction in Merkel cells, reveal unexpected functions for these cells in touch, and support a revised, two-receptor site model of mechanosensory transduction.

Coculture system of keratinocytes and dorsal-root-ganglion-derived cells for screening neurotrophic factors involved in guidance of neuronal axon growth in the skin.

The density of peripheral nerve fibres is increased in atopic dermatitis. Moreover, reduction in the fibres in a mouse model of atopic dermatitis reduces scratching behaviour. Thus, regulation of nerve fibre extension could be an effective strategy to reduce itching in pruritus dermatosis. In this study, we established a new coculture system of keratinocytes and dorsal-root-ganglion-derived cells using an apparatus, AXIS(™) , which consists of two different channels connected via a set of microgrooves, through which signalling molecules and axons, but not living cells, can pass. When we seeded keratinocytes in one chamber, extension of nerve fibres was observed from dorsal root ganglion cells seeded in the other chamber. Addition of anti-BDNF antibody in the keratinocyte-seeded chamber significantly reduced the extension. Application of Semaphorin 3A also reduced the extension by approximately 50%. We suggest that this coculture system may be useful for screening of anti-itching drugs.

Frontiers in epidermal barrier homeostasis--an approach to mathematical modelling of epidermal calcium dynamics.

Intact epidermal barrier function is crucial for survival and is associated with the presence of gradients of both calcium ion concentration and electric potential. Although many molecules, including ion channels and pumps, are known to contribute to maintenance of these gradients, the mechanisms involved in epidermal calcium ion dynamics have not been clarified. We have established that a variety of neurotransmitters and their receptors, originally found in the brain, are expressed in keratinocytes and are also associated with barrier homeostasis. Moreover, keratinocytes and neurons show some similarities of electrochemical behaviour. As mathematical modelling and computer simulation have been employed to understand electrochemical phenomena in brain science, we considered that a similar approach might be applicable to describe the dynamics of epidermal electrochemical phenomena associated with barrier homeostasis. Such methodology would also be potentially useful to address a number of difficult problems in clinical dermatology, such as ageing and itching. Although this work is at a very early stage, in this essay, we discuss the background to our approach and we present some preliminary results of simulation of barrier recovery.

External negative electric potential accelerates exocytosis of lamellar bodies in human skin ex vivo.

Exocytosis of lamellar bodies at the uppermost nucleated layer of the epidermis is a crucial process for epidermal permeability barrier homoeostasis. We have previously suggested that skin surface electric potential might be associated with barrier homoeostasis. Thus, we hypothesized that the potential might drive exocytosis of lamellar bodies. In this study, we tested this idea by applying negative electric potential (-0.5 V) to human skin samples ex vivo for 2 h and observing the ultrastructure of the uppermost layer. The secretion of lamellar bodies was accelerated in the potential-applied skin, compared to that in untreated control skin. Multiphoton observation indicated that extracellular lipid domains were more extensive in treated skin than in control skin. Moreover, the calcium ion gradient was greater at the uppermost layer of the epidermis of treated skin, compared to that in control skin. These results indicate that electric potential may regulate lamellar body secretion in healthy human skin.

Distinct intracellular calcium responses of individual cultured human keratinocytes to air pressure changes.

BACKGROUND: We previously showed that application of hydraulic pressure to cultured human keratinocytes induced elevation of intracellular calcium concentration ([Ca(2+) ]i ), but the absolute value of the pressure could not be determined. PURPOSE: To evaluate the effect of the absolute value of pressure on keratinocytes and other skin cells. METHODS: In the present work, we examined the effect of changes in absolute pressure level by observing the [Ca(2+) ]i responses of cultured human keratinocytes and other cells cultured at the bottom of a hermetically sealed plastic flask as the air pressure in the flask was increased gradually, held stable, and then decreased abruptly, using the Ca(2+) -indicator fura-2. RESULTS: We found that the [Ca(2+) ]i of differentiated keratinocytes was changed significantly in each phase, whereas undifferentiated keratinocytes and other cells derived from skin or dorsal root ganglion showed no response. Removal of calcium from the medium blocked the increase in [Ca(2+) ]i in differentiated keratinocytes. The [Ca(2+) ]i responses of individual differentiated keratinocytes in the increasing, stable and decreasing phases of pressure change varied from cell to cell. The threshold of air-pressure increase from the original level for inducing [Ca(2+) ]i response was 5 - 20 hPa. CONCLUSION: These results suggest that epidermal keratinocytes might contain a sensory system that detects changes of external pressure on the skin.

Softness sensor system for simultaneously measuring the mechanical properties of superficial skin layer and whole skin.

BACKGROUND/AIMS: Few attempts have been made to distinguish the softness of different skin layers, though specific measurement of the superficial layer would be useful for evaluating the emollient effect of cosmetics and for diagnosis of skin diseases. MATERIALS AND METHODS: We developed a sensor probe consisting of a piezoelectric tactile sensor and a load cell. To evaluate it, we firstly measured silicone rubber samples with different softness. Then, it was applied to human forearm skin before and after tape-stripping. A VapoMeter and skin-surface hygrometer were used to confirm removal of the stratum corneum. A Cutometer was used to obtain conventional softness data for comparison. RESULTS AND CONCLUSIONS: Both the piezoelectric tactile sensor and the load cell could measure the softness of silicone rubber samples, but the piezoelectric tactile sensor was more sensitive than the load cell when the reaction force of the measured sample was under 100 mN in response to a 2-mm indentation. For human skin in vivo, transepidermal water loss and skin conductance were significantly changed after tape-stripping, confirming removal of the stratum corneum. The piezoelectric tactile sensor detected a significant change after tape-stripping, whereas the load cell did not. Thus, the piezoelectric tactile sensor can detect changes of mechanical properties at the skin surface. The load cell data were in agreement with Cutometer measurements, which showed no change in representative skin elasticity parameters after tape-stripping. These results indicate that our sensor can simultaneously measure the mechanical properties of the superficial skin layer and whole skin.

Skin Cold Stimulation Can Modulate the Perceptual Rating of Musical Chords.

We studied the effect of cutaneous cold stimulus on the perceptual rating of musical chords. Despite the shown influence of music and tactile stimuli on human psychological evaluation, the effect of a cold stimulus on sound perception remains underexplored. We examined the effect of a cold stimulus on four psychological measures (frisson, arousal, pleasantness, and valence) as participants listened to two-note chords (consonance and dissonance). The cold-stimulus condition involved an experimenter touching the back of the participant's neck with a cooling device while listening to the sounds, while the control condition used a cooling device with the power off. For the frisson and arousal measures, the main effect of the stimulus condition was significant, showing that the cold stimulus increased the frisson and arousal measures. For the pleasantness and valence measures, there was a significant main effect of two-note chords, showing that a consonance was perceived as more pleasant than a dissonance; however, there was no significant main effect of stimulus condition, showing that the cold stimulus did not affect pleasantness and valence ratings. The results showed that a cold stimulus could bias frisson and arousal without affecting pleasantness and valence ratings when listening to musical sound.

Effects of N-acetyl-L-tryptophan on desorption of the protein-bound uremic toxin indoxyl sulfate and effects on uremic sarcopenia.

INTRODUCTION: Indoxyl sulfate (IS) is a protein-bound uremic toxin that causes uremic sarcopenia. IS has poor dialysis clearance; however, the addition of a binding competitor improves its removal efficiency. METHODS: Dialysis experiments were performed using N-acetyl-l-tryptophan (L-NAT) instead of l-tryptophan (Trp) using pooled sera obtained from dialysis patients. The molecular structures of L-NAT and Trp were similar to that of IS. Therefore, we examined whether Trp and L-NAT were involved in muscle atrophy in the same manner as IS by performing culture experiments using a human myotube cell line. RESULTS: The removal efficiency of L-NAT was the same as that of Trp. However, L-NAT concentrations in the pooled sera increased at the end of the experiment. Trp (1 mM) decreased the area of human myocytes, similar to IS, whereas L-NAT did not. CONCLUSION: L-NAT is a binding competitor with the ability to remove protein-bound IS while preventing sarcopenia.

Blockade of glucagon increases muscle mass and alters fiber type composition in mice deficient in proglucagon-derived peptides.

AIMS/INTRODUCTION: Glucagon is secreted from pancreatic α-cells and plays an important role in amino acid metabolism in liver. Various animal models deficient in glucagon action show hyper-amino acidemia and α-cell hyperplasia, indicating that glucagon contributes to feedback regulation between the liver and the α-cells. In addition, both insulin and various amino acids, including branched-chain amino acids and alanine, participate in protein synthesis in skeletal muscle. However, the effect of hyperaminoacidemia on skeletal muscle has not been investigated. In the present study, we examined the effect of blockade of glucagon action on skeletal muscle using mice deficient in proglucagon-derived peptides (GCGKO mice). MATERIALS AND METHODS: Muscles isolated from GCGKO and control mice were analyzed for their morphology, gene expression and metabolites. RESULTS: GCGKO mice showed muscle fiber hypertrophy, and a decreased ratio of type IIA and an increased ratio of type IIB fibers in the tibialis anterior. The expression levels of myosin heavy chain (Myh) 7, 2, 1 and myoglobin messenger ribonucleic acid were significantly lower in GCGKO mice than those in control mice in the tibialis anterior. GCGKO mice showed a significantly higher concentration of arginine, asparagine, serine and threonine in the quadriceps femoris muscles, and also alanine, aspartic acid, cysteine, glutamine, glycine and lysine, as well as four amino acids in gastrocnemius muscles. CONCLUSIONS: These results show that hyperaminoacidemia induced by blockade of glucagon action in mice increases skeletal muscle weight and stimulates slow-to-fast transition in type II fibers of skeletal muscle, mimicking the phenotype of a high-protein diet.