Bio-Impedance Sensor for Real-Time Artery Diameter Waveform Assessment

The real-time artery diameter waveform assessment during cardio cycle can allow the measurement of beat-to-beat pressure change and the long-term blood pressure monitoring. The aim of this study is to develop a self-calibrated bio-impedance-based sensor, which can provide regular measurement of the blood-pressure-dependence time variable parameters such as the artery diameter waveform and the elasticity. This paper proposes an algorithm based on analytical models which need prior geometrical and physiological patient parameters for more appropriate electrode system selection and hence location to provide accurate blood pressure measurement. As a result of this study, the red cell orientation effect contribution was estimated and removed from the bio-impedance signal obtained from the artery to keep monitoring the diameter waveform correspondence to the change of blood pressure.

Melt electro-written scaffolds with box-architecture support orthogonally-oriented collagen

Melt Electro-Writing (MEW) is a state-of-the-art technique that supports fabrication of 3D, precisely controlled and reproducible fiber structures. A standard MEW scaffold design is a box-structure, where a repeat layer of 90° boxes is produced from a single fiber. In 3D form (i.e., multiple layers), this structure has the potential to mimic orthogonal arrangements of collagen, as observed in the corneal stroma. In this study, we determined the response of human primary corneal stromal cells and their deposited fibrillar collagen (detected using a CNA35 probe) following 6-weeks in vitro culture on these box-structures made from poly(ε-caprolactone). Comparison was also made to glass substrates (topography-free) and electrospun poly(ε-caprolactone) fibers (aligned topography). Cell orientation and collagen deposition were non-uniform on glass substrates. Electrospun scaffolds supported an excellent parallel arrangement of cells and deposited collagen to the underlying architecture of aligned fibers, but there was no evidence of bidirectional collagen. In contrast, MEW scaffolds encouraged the formation of a dense, interconnected cellular network and deposited fibrillar collagen layers with a distinct orthogonal-arrangement. Collagen fibrils were particularly dominant through the middle layers of the MEW scaffolds’ total thickness and closer examination revealed these fibrils to be concentrated within the pores’ central regions. With the demand for donor corneas far exceeding the supply - leaving many with visual impairment - the application of MEW as a potential technique to recreate the corneal stroma with spontaneous, bidirectional collagen organization warrants further study.

Locus-Conserved Circular RNA cZNF292 Controls Endothelial Cell Flow Responses

Background : Circular RNAs (circRNAs) are generated by back-splicing of mostly mRNAs and are gaining increasing attention as a novel class of regulatory RNAs that control various cellular functions. However, their physiological roles and functional conservation in vivo are rarely addressed, given the inherent challenges of their genetic inactivation. Here we aimed to identify locus conserved circRNAs in mice and humans, which can be genetically deleted due to retained intronic elements not contained in the mRNA host gene to eventually address functional conservation. Methods: Mechanistically, we identified the protein syndesmos (SDOS) to specifically interact with cZNF292 in endothelial cells by RNA affinity purification and subsequent mass spectrometry analysis. Silencing of SDOS or its protein binding partner Syndecan-4, or mutation of the SDOS-cZNF292 binding site, prevented laminar flow-induced cytoskeletal reorganisation thereby recapitulating cZfp292 phenotypes. Results: Combining published endothelial RNA sequencing datasets with circRNAs of the circATLAS databank, we identified locus-conserved circRNA retaining intronic elements between mice and humans. CRISPR/Cas9 mediated genetic depletion of the top expressed circRNA cZfp292 resulted in an altered endothelial morphology and aberrant flow alignment in the aorta in vivo. Consistently, depletion of cZNF292 in endothelial cells in vitro abolished laminar flow-induced alterations in cell orientation, paxillin localisation and focal adhesion organisation. Conclusion: Together, our data reveal a hitherto unknown role of cZNF292/cZfp292 in endothelial flow responses, which influences endothelial shape.

Propagating acoustic waves on a culture substrate regulate the directional collective cell migration

Collective cell migration plays a critical role in physiological and pathological processes such as development, wound healing, and metastasis. Numerous studies have demonstrated how various types of chemical, mechanical, and electrical cues dictate the collective migratory behaviors of cells. Although an acoustic cue can be advantageous because of its noninvasiveness and biocompatibility, cell migration in response to acoustic stimulation remains poorly understood. In this study, we developed a device that is able to apply surface acoustic waves to a cell culture substrate and investigated the effect of propagating acoustic waves on collective cell migration. The migration distance estimated at various wave intensities revealed that unidirectional cell migration was enhanced at a critical wave intensity and that it was suppressed as the intensity was further increased. The increased migration might be attributable to cell orientation alignment along the direction of the propagating wave, as characterized by nucleus shape. Thicker actin bundles indicative of a high traction force were observed in cells subjected to propagating acoustic waves at the critical intensity. Our device and technique can be useful for regulating cellular functions associated with cell migration.

Implication of Vestibular Hair Cell Loss of Planar Polarity for the Canal and Otolith-Dependent Vestibulo-Ocular Reflexes in Celsr1–/– Mice

Introduction: Vestibular sensory hair cells are precisely orientated according to planar cell polarity (PCP) and are key to enable mechanic-electrical transduction and normal vestibular function. PCP is found on different scales in the vestibular organs, ranging from correct hair bundle orientation, coordination of hair cell orientation with neighboring hair cells, and orientation around the striola in otolithic organs. Celsr1 is a PCP protein and a Celsr1 KO mouse model showed hair cell disorganization in all vestibular organs, especially in the canalar ampullae. The objective of this work was to assess to what extent the different vestibulo-ocular reflexes were impaired in Celsr1 KO mice.Methods: Vestibular function was analyzed using non-invasive video-oculography. Semicircular canal function was assessed during sinusoidal rotation and during angular velocity steps. Otolithic function (mainly utricular) was assessed during off-vertical axis rotation (OVAR) and during static and dynamic head tilts.Results: The vestibulo-ocular reflex of 10 Celsr1 KO and 10 control littermates was analyzed. All KO mice presented with spontaneous nystagmus or gaze instability in dark. Canalar function was reduced almost by half in KO mice. Compared to control mice, KO mice had reduced angular VOR gain in all tested frequencies (0.2–1.5 Hz), and abnormal phase at 0.2 and 0.5 Hz. Concerning horizontal steps, KO mice had reduced responses. Otolithic function was reduced by about a third in KO mice. Static ocular-counter roll gain and OVAR bias were both significantly reduced. These results demonstrate that canal- and otolith-dependent vestibulo-ocular reflexes are impaired in KO mice.Conclusion: The major ampullar disorganization led to an important reduction but not to a complete loss of angular coding capacities. Mildly disorganized otolithic hair cells were associated with a significant loss of otolith-dependent function. These results suggest that the highly organized polarization of otolithic hair cells is a critical factor for the accurate encoding of the head movement and that the loss of a small fraction of the otolithic hair cells in pathological conditions is likely to have major functional consequences. Altogether, these results shed light on how partial loss of vestibular information encoding, as often encountered in pathological situations, translates into functional deficits.

Effect of Gravity and Various Operating Conditions on Proton Exchange Membrane Water Electrolysis Cell Performance

Water electrolysis is an eco-friendly method for the utilization of renewable energy sources which provide intermittent power supply. Proton exchange membrane water electrolysis (PEMWE) has a high efficiency in this regard. However, the two-phase flow of water and oxygen at the anode side causes performance degradation, and various operating conditions affect the performance of PEMWE. In this study, the effects of four control parameters (operating temperature, flow rate, cell orientation, and pattern of the channel) on the performance of PEMWE were investigated. The effects of the operating conditions on its performance were examined using a 25 cm2 single-cell. Evaluation tests were conducted using in situ methods such as polarization curves and electrochemical impedance spectroscopy. The results demonstrated that a high operating temperature and low flow rate reduce the activation and ohmic losses, and thereby enhance the performance of PEMWE. Additionally, the cell orientation affects the performance of PEMWE owing to the variation in the two-phase flow regime. It was observed that the slope of specific sections in the polarization curve rapidly increases at a specific cell voltage.

Low cuticle deposition rate in ‘Apple’ mango increases elastic strain, weakens the cuticle and increases russet

Russeting compromises appearance and downgrades the market value of many fruitcrops, including of the mango cv. ‘Apple’. The objective was to identify the mechanistic basis of ‘Apple’ mango’s high susceptibility to russeting. We focused on fruit growth, cuticle deposition, stress/strain relaxation analysis and the mechanical properties of the cuticle. The non-susceptible mango cv. ‘Tommy Atkins’ served for comparison. Compared with ‘Tommy Atkins’, fruit of ‘Apple’ had a lower mass, a smaller surface area and a lower growth rate. There were little differences between the epidermal and hypodermal cells of ‘Apple’ and ‘Tommy Atkins’ including cell size, cell orientation and cell number. Lenticel density decreased during development, being lower in ‘Apple’ than in ‘Tommy Atkins’. The mean lenticel area increased during development but was consistently greater in ‘Apple’ than in ‘Tommy Atkins’. The deposition rate of the cuticular membrane was initially rapid but later slowed till it matched the area expansion rate, thereafter mass per unit area was effectively constant. The cuticle of ‘Apple’ is thinner than that of ‘Tommy Atkins’. Cumulative strain increased sigmoidally with fruit growth. Strains released stepwise on excision and isolation (εexc+iso), and on wax extraction (εextr) were higher in ‘Apple’ than in ‘Tommy Atkins’. Membrane stiffness increased during development being consistently lower in ‘Apple’ than in ‘Tommy Atkins’. Membrane fracture force (Fmax) was low and constant in developing ‘Apple’ but increased in ‘Tommy Atkin’. Membrane strain at fracture (εmax) decreased linearly during development but was lower in ‘Apple’ than in ‘Tommy Atkins’. Frequency of membrane failure associated with lenticels increased during development and was consistently higher in ‘Apple’ than in ‘Tommy Atkins’. The lower rate of cuticular deposition, the higher strain releases on excision, isolation and wax extraction and the weaker cuticle account for the high russet susceptibility of ‘Apple’ mango.

Brain microvasculature endothelial cell orientation on micropatterned hydrogels is affected by glucose level variations

This work reports on an effort to decipher the alignment of brain microvasculature endothelial cells to physical constrains generated via adhesion control on hydrogel surfaces and explore the corresponding responses upon glucose level variations emulating the hypo- and hyperglycaemic effects in diabetes. We prepared hydrogels of hyaluronic acid a natural biomaterial that does not naturally support endothelial cell adhesion, and specifically functionalised RGD peptides into lines using UV-mediated linkage. The width of the lines was varied from 10 to 100 µm. We evaluated cell alignment by measuring the nuclei, cell, and F-actin orientations, and the nuclei and cell eccentricity via immunofluorescent staining and image analysis. We found that the brain microvascular endothelial cells aligned and elongated to these physical constraints for all line widths. In addition, we also observed that varying the cell medium glucose levels affected the cell alignment along the patterns. We believe our results may provide a platform for further studies on the impact of altered glucose levels in cardiovascular disease.

A Reversal in Hair Cell Orientation Organizes Both the Auditory and Vestibular Organs

Sensory hair cells detect mechanical stimuli with their hair bundle, an asymmetrical brush of actin-based membrane protrusions, or stereocilia. At the single cell level, stereocilia are organized in rows of graded heights that confer the hair bundle with intrinsic directional sensitivity. At the organ level, each hair cell is precisely oriented so that its intrinsic directional sensitivity matches the direction of mechanical stimuli reaching the sensory epithelium. Coordinated orientation among neighboring hair cells usually ensures the delivery of a coherent local group response. Accordingly, hair cell orientation is locally uniform in the auditory and vestibular cristae epithelia in birds and mammals. However, an exception to this rule is found in the vestibular macular organs, and in fish lateral line neuromasts, where two hair cell populations show opposing orientations. This mirror-image hair cell organization confers bidirectional sensitivity at the organ level. Here I review our current understanding of the molecular machinery that produces mirror-image organization through a regional reversal of hair cell orientation. Interestingly, recent evidence suggests that auditory hair cells adopt their normal uniform orientation through a global reversal mechanism similar to the one at work regionally in macular and neuromast organs. Macular and auditory organs thus appear to be patterned more similarly than previously appreciated during inner ear development.