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Nature Communications Jun 2024Mammalian inner ear hair cell loss leads to permanent hearing and balance dysfunction. In contrast to the cochlea, vestibular hair cells of the murine utricle have some...
Mammalian inner ear hair cell loss leads to permanent hearing and balance dysfunction. In contrast to the cochlea, vestibular hair cells of the murine utricle have some regenerative capacity. Whether human utricular hair cells regenerate in vivo remains unknown. Here we procured live, mature utricles from organ donors and vestibular schwannoma patients, and present a validated single-cell transcriptomic atlas at unprecedented resolution. We describe markers of 13 sensory and non-sensory cell types, with partial overlap and correlation between transcriptomes of human and mouse hair cells and supporting cells. We further uncover transcriptomes unique to hair cell precursors, which are unexpectedly 14-fold more abundant in vestibular schwannoma utricles, demonstrating the existence of ongoing regeneration in humans. Lastly, supporting cell-to-hair cell trajectory analysis revealed 5 distinct patterns of dynamic gene expression and associated pathways, including Wnt and IGF-1 signaling. Our dataset constitutes a foundational resource, accessible via a web-based interface, serving to advance knowledge of the normal and diseased human inner ear.
Topics: Humans; Transcriptome; Single-Cell Analysis; Animals; Regeneration; Mice; Saccule and Utricle; Neuroma, Acoustic; Ear, Inner; Insulin-Like Growth Factor I; Male; Hair Cells, Vestibular; Female; Gene Expression Profiling
PubMed: 38844821
DOI: 10.1038/s41467-024-48491-y -
American Journal of Physiology.... Jul 2024The purpose of the present study was to clarify the impact of age on the sympathoinhibitory response to cardiopulmonary baroreceptor loading in females. Nine older... (Comparative Study)
Comparative Study
The purpose of the present study was to clarify the impact of age on the sympathoinhibitory response to cardiopulmonary baroreceptor loading in females. Nine older females (mean ± SD, 70 ± 6 yr) and 11 younger females (20 ± 1 yr) completed the study. A passive leg raising (PLR) test was performed wherein the participants were positioned supine (baseline, 0°), and their lower limbs were passively lifted at 10°, 20°, 30°, and 40° (3 min at each angle). Muscle sympathetic nerve activity (MSNA) was recorded via microneurography of the left radial nerve. The central venous pressure was estimated based on peripheral venous pressure (eCVP), which was monitored using a cannula in the right large antecubital vein. Baseline MSNA was higher in older females than in younger females. MSNA burst frequency (BF) decreased during the PLR test in both older and younger females, but the magnitude of the decrease in MSNA BF was smaller in older females than in younger females (older, -3.5 ± 1.5 vs. younger, -6.3 ± 1.5 bursts/min at 40° from baseline, = 0.014). The eCVP increased during the PLR in both groups, and there was no difference in the changes in eCVP between the two groups (older, +1.07 ± 0.37 vs. younger, +1.12 ± 0.33 mmHg at 40° from baseline, = 0.941). These results suggest that inhibition of sympathetic vasomotor outflow during cardiopulmonary baroreceptor loading could be blunted with advancing age in females. There were no available data concerning the effect of age on the sympathoinhibitory response to cardiopulmonary baroreceptor loading in females. The magnitude of the decrease in muscle sympathetic nerve activity during passive leg raising (10°-40°) was smaller in older females than in young females. In females, inhibition of sympathetic vasomotor outflow during cardiopulmonary baroreceptor loading could be blunted with advancing age.
Topics: Humans; Female; Sympathetic Nervous System; Pressoreceptors; Aged; Aging; Baroreflex; Young Adult; Muscle, Skeletal; Age Factors; Blood Pressure; Middle Aged; Lung; Neural Inhibition
PubMed: 38842517
DOI: 10.1152/ajpregu.00109.2024 -
Science (New York, N.Y.) May 2024Human skin sensing of mechanical stimuli originates from transduction of mechanoreceptors that converts external forces into electrical signals. Although imitating the...
Human skin sensing of mechanical stimuli originates from transduction of mechanoreceptors that converts external forces into electrical signals. Although imitating the spatial distribution of those mechanoreceptors can enable developments of electronic skins capable of decoupled sensing of normal/shear forces and strains, it remains elusive. We report a three-dimensionally (3D) architected electronic skin (denoted as 3DAE-Skin) with force and strain sensing components arranged in a 3D layout that mimics that of Merkel cells and Ruffini endings in human skin. This 3DAE-Skin shows excellent decoupled sensing performances of normal force, shear force, and strain and enables development of a tactile system for simultaneous modulus/curvature measurements of an object through touch. Demonstrations include rapid modulus measurements of fruits, bread, and cake with various shapes and degrees of freshness.
Topics: Humans; Mechanoreceptors; Merkel Cells; Skin; Skin Physiological Phenomena; Skin, Artificial; Touch; Wearable Electronic Devices
PubMed: 38815009
DOI: 10.1126/science.adk5556 -
Development (Cambridge, England) May 2024The planar polarized organization of hair cells in the vestibular maculae is unique because these sensory organs contain two groups of cells with oppositely oriented...
The planar polarized organization of hair cells in the vestibular maculae is unique because these sensory organs contain two groups of cells with oppositely oriented stereociliary bundles that meet at a line of polarity reversal (LPR). EMX2 is a transcription factor expressed by one hair cell group that reverses the orientation of their bundles, thereby forming the LPR. We generated Emx2-CreERt2 transgenic mice for genetic lineage tracing and demonstrate Emx2 expression before hair cell specification when the nascent utricle and saccule constitute a continuous prosensory domain. Precursors labeled by Emx2-CreERt2 at this stage give rise to hair cells located along one side of the LPR in the mature utricle or saccule, indicating that this boundary is first established in the prosensory domain. Consistent with this, Emx2-CreERt2 lineage tracing in Dreher mutants, where the utricle and saccule fail to segregate, labels a continuous field of cells along one side of a fused utriculo-saccular-cochlear organ. These observations reveal that LPR positioning is pre-determined in the developing prosensory domain, and that EMX2 expression defines lineages of hair cells with oppositely oriented stereociliary bundles.
Topics: Animals; Homeodomain Proteins; Mice; Mice, Transgenic; Cell Lineage; Transcription Factors; Ear, Inner; Cell Polarity; Saccule and Utricle; Gene Expression Regulation, Developmental; Hair Cells, Auditory
PubMed: 38804528
DOI: 10.1242/dev.202425 -
Journal of Psychiatry and Cognitive... 2024Opioid use disorder (OUD)-associated overdose deaths have reached epidemic proportions worldwide. An important driving force for relapse is anxiety associated with...
OBJECTIVES
Opioid use disorder (OUD)-associated overdose deaths have reached epidemic proportions worldwide. An important driving force for relapse is anxiety associated with opioid withdrawal. We hypothesized that our new technology, termed heterodyned whole-body vibration (HWBV) would ameliorate anxiety associated with OUD.
METHODS
Using a randomized, placebo (sham)-controlled, double-blind study design in an NIH-sponsored Phase 1 trial, we evaluated 60 male and 26 female participants diagnosed with OUD and undergoing treatment at pain and rehabilitation clinics. We utilized the Hamilton Anxiety Scale (HAM-A) and a daily visual analog scale anxiety rating (1-10) to evaluate anxiety. Subjects were treated for 10 min 5X/week for 4 weeks with either sham vibration (no interferential beat or harmonics) or HWBV (beats and harmonics). The participants also completed a neuropsychological test battery at intake and discharge.
RESULTS
In OUD subjects with moderate anxiety, there was a significant improvement in daily anxiety scores in the HWBV group compared to the sham treatment group (p=3.41 × 10). HAM-A scores in OUD participants at intake showed moderate levels of anxiety in OUD participants (HWBV group: 15.9 ± 1.6; Sham group: 17.8 ± 1.6) and progressively improved in both groups at discharge, but improvement was greater in the HWBV group (p=1.37 × 10). Furthermore, three indices of neuropsychological testing (mental rotations, spatial planning, and response inhibition) were significantly improved by HWBV treatment.
CONCLUSIONS
These findings support HWBV as a novel, non-invasive, non-pharmacological treatment for anxiety associated with OUD.
PubMed: 38798753
DOI: 10.29011/2574-7762.000073 -
International Journal of Molecular... May 2024The synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) are the most vulnerable structures in the noise-exposed cochlea. Cochlear synaptopathy...
The synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) are the most vulnerable structures in the noise-exposed cochlea. Cochlear synaptopathy results from the disruption of these synapses following noise exposure and is considered the main cause of poor speech understanding in noisy environments, even when audiogram results are normal. Cochlear synaptopathy leads to the degeneration of SGNs if damaged IHC-SGN synapses are not promptly recovered. Oxidative stress plays a central role in the pathogenesis of cochlear synaptopathy. C-Phycocyanin (C-PC) has antioxidant and anti-inflammatory activities and is widely utilized in the food and drug industry. However, the effect of the C-PC on noise-induced cochlear damage is unknown. We first investigated the therapeutic effect of C-PC on noise-induced cochlear synaptopathy. In vitro experiments revealed that C-PC reduced the HO-induced generation of reactive oxygen species in HEI-OC1 auditory cells. HO-induced cytotoxicity in HEI-OC1 cells was reduced with C-PC treatment. After white noise exposure for 3 h at a sound pressure of 118 dB, the guinea pigs intratympanically administered 5 μg/mL C-PC exhibited greater wave I amplitudes in the auditory brainstem response, more IHC synaptic ribbons and more IHC-SGN synapses according to microscopic analysis than the saline-treated guinea pigs. Furthermore, the group treated with C-PC had less intense 4-hydroxynonenal and intercellular adhesion molecule-1 staining in the cochlea compared with the saline group. Our results suggest that C-PC improves cochlear synaptopathy by inhibiting noise-induced oxidative stress and the inflammatory response in the cochlea.
Topics: Animals; Oxidative Stress; Guinea Pigs; Phycocyanin; Cochlea; Synapses; Noise; Intercellular Adhesion Molecule-1; Hearing Loss, Noise-Induced; Reactive Oxygen Species; Male; Spiral Ganglion; Hydrogen Peroxide; Hair Cells, Auditory, Inner; Antioxidants; Cell Line; Hearing Loss, Hidden
PubMed: 38791192
DOI: 10.3390/ijms25105154 -
Biology May 2024Statocyst anatomy and fine morphology in Norwegian lobster () are studied for the first time using scanning and transmission electron microscopy. exhibits sensory setae...
Statocyst anatomy and fine morphology in Norwegian lobster () are studied for the first time using scanning and transmission electron microscopy. exhibits sensory setae projecting from the statocyst inner cavity floor into a mass of sand granules (statoconia) embedded in a gelatinous substance. The setae are distributed in four areas: a curved field made up of an inner single row and an outer double row that run on a circle around the medial and lateral rim of the central depression, a small setal field in the posterior part, a large setal field, opposite to the small field, and a short row, running internally and lying parallel to the inner single row, next to the small setal field. A study of the fine morphology of the statocyst sensory setae shows that the structure of the setae in the different areas is similar, with a bulb (the proximal portion of the sensillum), a setal shaft, a tooth (the smooth portion of the bulb), a fulcrum (a transverse fold), and filamentous hairs. The hair cells are firmly implanted within the cuticular layer. Although the type of innervation of the statocyst was not determined in the present study, the close taxonomic position of the lobster to that of the crayfish and crab would suggest that the setae in are pure mechanoreceptors rather than sensory cells.
PubMed: 38785807
DOI: 10.3390/biology13050325 -
Journal of Morphology Jun 2024The incisor teeth in pigs, Sus scrofa, function in association with a disc-shaped snout to explore the environment for potential food. Understanding how mechanical...
The incisor teeth in pigs, Sus scrofa, function in association with a disc-shaped snout to explore the environment for potential food. Understanding how mechanical loading applied to the tooth deforms the periodontal ligament (PDL) is important to determining the role of periodontal mechanoreceptors during food exploration and feeding. The objective of this study was to use fiber Bragg (FBG) sensors to measure strain in vivo within the PDL space of pig incisors. The central mandibular incisors of pigs underwent spring loaded lingual tipping during FBG strain recording within the labial periodontal space. FBG sensors were placed within the periodontal space of the central mandibular incisors of ~2-3-month-old farm pigs. The magnitude and orientation of spring loads are expected to mimic incisor contact with food. During incisor tipping with load calibrated springs, FBG strains in vitro (N = 6) and in vivo (N = 6) recorded at comparable load levels overlapped in range (-10-20 με). Linear regressions between peak FBG strains, that is, the highest recorded strain value, and baseline strains, that is, strain without applied spring load, were significant across all in vivo experiments (peak strain at 200 g vs. baseline, p = .04; peak strain at 2000 g vs. baseline p = .03; peak strain at 2000 g vs. 200 g, p = .004). These linear relationships indicate that on a per experiment basis, the maximum measured strain at different spring loads showed predictable differences. A Friedman test of the absolute value of peak strain confirmed the significant increase in strain between baseline, 200 g, and 2000 g spring activation (p = .02). Mainly compressive strains were recorded in the labial PDL space and increases in spring load applied in vivo generated increases in FBG strain measurements. These results demonstrate the capacity for FBG sensors to be used in vivo to assess transmission of occlusal loads through the periodontium. PDL strain is associated with mechanoreceptor stimulation and is expected to affect the functional morphology of the incisors. The overall low levels of strain observed may correspond with the robust functional morphology of pig incisors and the tendency for pigs to encounter diverse foods and substrates during food exploration.
Topics: Animals; Incisor; Periodontal Ligament; Stress, Mechanical; Swine; Sus scrofa; Biomechanical Phenomena
PubMed: 38783683
DOI: 10.1002/jmor.21738 -
Non-equilibrium compression achieving high sensitivity and linearity for iontronic pressure sensors.Science Bulletin May 2024Flexible pressure sensors with high sensitivity and linearity are highly desirable for robot sensing and human physiological signal detection. However, the current...
Flexible pressure sensors with high sensitivity and linearity are highly desirable for robot sensing and human physiological signal detection. However, the current strategies for stabilizing axial microstructures (e.g., micro-pyramids) are mainly susceptible to structural stiffening during compression, thereby limiting the realization of high sensitivity and linearity. Here, we report a bending-induced non-equilibrium compression process that effectively enhances the compressibility of microstructures, thereby crucially improving the efficiency of interfacial area growth of electric double layer (EDL). Based on this principle, we fabricate an iontronic flexible pressure sensor with vertical graphene (VG) array electrodes. Ultra-high sensitivity (185.09 kPa) and linearity (R = 0.9999) are realized over a wide pressure range (0.49 Pa-66.67 kPa). It also exhibits remarkable mechanical stability during compression and bending. The sensor is successfully employed in a robotic gripping task to recognize the targets of different materials and shapes based on a multilayer perception (MLP) neural network. It opens the door to realizing haptic sensing capabilities for robotic hands and prosthetic limbs.
PubMed: 38782658
DOI: 10.1016/j.scib.2024.05.001 -
Biomaterials Science Jun 2024Bone injury is often associated with tears in the periosteum and changes in the internal stress microenvironment of the periosteum. In this study, we investigated the...
Bone injury is often associated with tears in the periosteum and changes in the internal stress microenvironment of the periosteum. In this study, we investigated the biological effects of periosteal prestress release on periosteum-derived cells (PDCs) and the potential mechanisms of endogenous stem cell recruitment. Decellularized periosteum with natural extracellular matrix (ECM) components was obtained by a combination of physical, chemical, and enzymatic decellularization. The decellularized periosteum removed immunogenicity while retaining the natural network structure and composition of the ECM. The Young's modulus has no significant difference between the periosteum before and after decellularization. The extracted PDCs were further composited with the decellularized periosteum and subjected to 20% stress release. It was found that the proliferative capacity of PDCs seeded on decellularized periosteum was significantly enhanced 6 h after stress release of the periosteum. The cell culture supernatant obtained after periosteal prestress release was able to significantly promote the migration ability of PDCs within 24 h. Enzyme-linked immunosorbnent assay (ELISA) experiments showed that the expression of stroma-derived factor-1α (SDF-1α) and vascular endothelial growth factor (VEGF) in the supernatant increased significantly after 3 h and 12 h of stress release, respectively. Furthermore, periosteal stress release promoted the high expression of osteogenic markers osteocalcin (OCN), osteopontin (OPN), and collagen type I of PDCs. The change in stress environment caused by the release of periosteal prestress was sensed by integrin β1, a mechanoreceptor on the membrane of PDCs, which further stimulated the expression of YAP in the nucleus. These investigations provided a novel method to evaluate the importance of mechanical stimulation in periosteum, which is also of great significance for the design and fabrication of artificial periosteum with mechanical regulation function.
Topics: Periosteum; Cell Proliferation; Osteogenesis; Cell Differentiation; Cell Movement; Stress, Mechanical; Animals; Extracellular Matrix; Cells, Cultured; Humans; Tissue Engineering
PubMed: 38771565
DOI: 10.1039/d4bm00358f