scholarly journals Ultrasound mediated cellular deflection results in cellular depolarization

2021 ◽  
Author(s):  
Aditya Vasan ◽  
Jeremy Orosco ◽  
Uri Magaram ◽  
Connor Weiss ◽  
Marc Duque ◽  
...  
Keyword(s):  
High Speed ◽  
Biomechanical Model ◽  
Cellular Membrane ◽  
Membrane Dynamics ◽  
Membrane Voltage ◽  
Digital Holographic Microscopy ◽  
Neuronal Membrane ◽  
Ultrasound Stimulation ◽  
Whole Cell Patch Clamp ◽  
Patch Clamp Electrophysiology

Ultrasound has been used to manipulate cells in both humans and animal models. While intramembrane cavitation and lipid clustering have been suggested as likely mechanisms, they lack experimental evidence. Here we use high-speed digital holographic microscopy (to 100-kHz order) to visualize the cellular membrane dynamics. We show that neuronal and fibroblast membranes deflect about 150 nm upon ultrasound stimulation. Next, we develop a biomechanical model that predicts changes in membrane voltage after ultrasound exposure. Finally, we validate our model predictions using whole-cell patch clamp electrophysiology on primary neurons. Collectively, we show that ultrasound stimulation directly defects the neuronal membrane leading to a change in membrane voltage and subsequent depolarization. Our model is consistent with existing data and provides a mechanism for both ultrasound-evoked neurostimulation and sonogenetic control.

scholarly journals Inhibitors of VPS34 and lipid metabolism suppress SARS-CoV-2 replication

2020 ◽  
Author(s):  
Jesus A. Silvas ◽  
Alexander S. Jureka ◽  
Anthony M. Nicolini ◽  
Stacie A. Chvatal ◽  
Christopher F. Basler
Keyword(s):  
Lipid Metabolism ◽  
Fatty Acid Synthetase ◽  
Cellular Membrane ◽  
Fatty Acyl ◽  
Membrane Dynamics ◽  
Epithelial Cell Line ◽  
Airway Epithelial ◽  
Virus Growth ◽  
Membrane Biology ◽  
Triacsin C

ABSTRACTTherapeutics targeting replication of SARS coronavirus 2 (SARS-CoV-2) are urgently needed. Coronaviruses rely on host membranes for entry, establishment of replication centers and egress. Compounds targeting cellular membrane biology and lipid biosynthetic pathways have previously shown promise as antivirals and are actively being pursued as treatments for other conditions. Here, we tested small molecule inhibitors that target membrane dynamics or lipid metabolism. Included were inhibitors of the PI3 kinase VPS34, which functions in autophagy, endocytosis and other processes; Orlistat, an inhibitor of lipases and fatty acid synthetase, is approved by the FDA as a treatment for obesity; and Triacsin C which inhibits long chain fatty acyl-CoA synthetases. VPS34 inhibitors, Orlistat and Triacsin C inhibited virus growth in Vero E6 cells and in the human airway epithelial cell line Calu-3, acting at a post-entry step in the virus replication cycle. Of these the VPS34 inhibitors exhibit the most potent activity.

scholarly journals Feeding mechanics and bite force modelling of the skull of Dunkleosteus terrelli , an ancient apex predator

2006 ◽  
Vol 3 (1) ◽  
pp. 77-80 ◽  
Author(s):  
Philip S.L Anderson ◽  
Mark W Westneat
Keyword(s):  
High Speed ◽  
Prey Capture ◽  
Mouth Opening ◽  
Biomechanical Model ◽  
Bite Force ◽  
Rapid Expansion ◽  
Large Individual ◽  
Linkage Mechanism ◽  
Feeding Mechanics ◽  
Four Bar Linkage

Placoderms are a diverse group of armoured fishes that dominated the aquatic ecosystems of the Devonian Period, 415–360 million years ago. The bladed jaws of predators such as Dunkleosteus suggest that these animals were the first vertebrates to use rapid mouth opening and a powerful bite to capture and fragment evasive prey items prior to ingestion. Here, we develop a biomechanical model of force and motion during feeding in Dunkleosteus terrelli that reveals a highly kinetic skull driven by a unique four-bar linkage mechanism. The linkage system has a high-speed transmission for jaw opening, producing a rapid expansion phase similar to modern fishes that use suction during prey capture. Jaw closing muscles power an extraordinarily strong bite, with an estimated maximal bite force of over 4400 N at the jaw tip and more than 5300 N at the rear dental plates, for a large individual (6 m in total length). This bite force capability is the greatest of all living or fossil fishes and is among the most powerful bites in animals.

scholarly journals Effect of Geraniol and Citronellol Essential Oils on the Biophysical Gating Properties of AMPA Receptors

2019 ◽  
Vol 9 (21) ◽  
pp. 4693 ◽  
Author(s):  
Mohammad Qneibi ◽  
Nidal Jaradat ◽  
Nour Emwas
Keyword(s):  
Essential Oils ◽  
Ampa Receptors ◽  
Neurological Diseases ◽  
Whole Cell Patch Clamp ◽  
293 Cells ◽  
Future Drug ◽  
Drug Synthesis ◽  
Patch Clamp Electrophysiology ◽  
Calming Effect ◽  
Natural Template

Essential oils have been advertised endlessly to be very beneficial for the health of humans, and an extensive amount of research examines the validity of such claims. In contribution, the current study evaluates the neuroprotective properties of Citronellol and Geraniol essential oils (EOs). In relationship to the biophysical gating properties of different the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunits, the EOs were administered to HEK293 (Human embryonic kidney 293) cells and examined for any inhibition and effect on desensitization or deactivation rates, using whole-cell patch-clamp electrophysiology. Our results demonstrated the highest levels of inhibition from Citronellol oil by four-fold on all AMPARs subunits. Likewise, Geraniol oil had a similar inhibiting impact on the receptors, and both oils decreased the desensitization and deactivation rates of the inhibited receptors. Thus, the examined EOs of this study portray neuroprotective qualities by targeting AMPARs activation and reducing desensitization and deactivation rates. Finally, the results of the current study entail a better understanding of AMPARs, provides a natural template for future drug synthesis to treat neurological diseases associated with excessive AMPAR activation, and offers a possible mechanism by which these essential oils deploy their ‘calming’ effect.

scholarly journals Impact of Different Developmental Instars on Locusta migratoria Jumping Performance

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Xiaojuan Mo ◽  
Donato Romano ◽  
Mario Milazzo ◽  
Giovanni Benelli ◽  
Wenjie Ge ◽  
...  
Keyword(s):  
High Speed ◽  
Developmental Stages ◽  
Locusta Migratoria ◽  
Biomechanical Model ◽  
Elastic Parameter ◽  
Leg Length ◽  
Jumping Performance ◽  
Locomotion Behavior ◽  
Geometrical Data ◽  
Jumping Robot

Ontogenetic locomotion research focuses on the evolution of locomotion behavior in different developmental stages of a species. Unlike vertebrates, ontogenetic locomotion in invertebrates is poorly investigated. Locusts represent an outstanding biological model to study this issue. They are hemimetabolous insects and have similar aspects and behaviors in different instars. This research is aimed at studying the jumping performance of Locusta migratoria over different developmental instars. Jumps of third instar, fourth instar, and adult L. migratoria were recorded through a high-speed camera. Data were analyzed to develop a simplified biomechanical model of the insect: the elastic joint of locust hind legs was simplified as a torsional spring located at the femur-tibiae joint as a semilunar process and based on an energetic approach involving both locomotion and geometrical data. A simplified mathematical model evaluated the performances of each tested jump. Results showed that longer hind leg length, higher elastic parameter, and longer takeoff time synergistically contribute to a greater velocity and energy storing/releasing in adult locusts, if compared to young instars; at the same time, they compensate possible decreases of the acceleration due to the mass increase. This finding also gives insights for advanced bioinspired jumping robot design.

scholarly journals Interferon γ Gene Expression in Sensory Neurons: Evidence for Autocrine Gene Regulation

1997 ◽  
Vol 186 (12) ◽  
pp. 2023-2031 ◽  
Author(s):  
Harald Neumann ◽  
Hannes Schmidt ◽  
Elke Wilharm ◽  
Lüder Behrens ◽  
Hartmut Wekerle
Keyword(s):  
Patch Clamp ◽  
Sensory Neurons ◽  
Nuclear Translocation ◽  
Interferon Γ ◽  
Dorsal Root Ganglion Neurons ◽  
Neuronal Membrane ◽  
Cultured Neurons ◽  
Ifn Γ ◽  
Patch Clamp Electrophysiology ◽  
Ganglion Neurons

We explored expression and possible function of interferon-γ (IFN-γ) in cultured fetal (E15) rat dorsal root ganglion neurons combining whole cell patch-clamp electrophysiology with single cell reverse transcriptase polymerase chain reaction and confocal laser immunocytochemistry. Morphologically, we located IFN-γ protein in the cytoplasm of the neurons in culture as well as in situ during peri- and postnatal development. Transcripts for classic IFN-γ and for its receptor were determined in probes of cytoplasm sampled from individual cultured neurons, which had been identified by patch clamp electrophysiology. In addition, the cultured neurons expressed both chains of the IFN-γ receptor. Locally produced IFN-γ acts back on its cellular source. Phosphorylation and nuclear translocation of the IFN-inducible transcriptional factor STAT1 as well as IFN-γ–dependent expression of major histocompatibility complex class I molecules on the neuronal membrane were noted in untreated cultures. However, both processes were substantially blocked in the presence of antibodies neutralizing IFN-γ. Our findings indicate a role of IFN-γ in autocrine regulation of sensory neurons.

Neuronal membrane dynamics as fine regulator of sphingolipid composition

2018 ◽  
Vol 35 (4) ◽  
pp. 397-402 ◽  
Author(s):  
Massimo Aureli ◽  
Maura Samarani ◽  
Nicoletta Loberto ◽  
Elena Chiricozzi ◽  
Laura Mauri ◽  
...  
Keyword(s):  
Membrane Dynamics ◽  
Neuronal Membrane

scholarly journals Distance- and activity-dependent modulation of spike back-propagation in layer V pyramidal neurons of the medial entorhinal cortex

2011 ◽  
Vol 105 (3) ◽  
pp. 1372-1379 ◽  
Author(s):  
Sonia Gasparini
Keyword(s):  
Entorhinal Cortex ◽  
High Speed ◽  
Pyramidal Neurons ◽  
Back Propagation ◽  
Medial Entorhinal Cortex ◽  
Type K ◽  
Whole Cell Patch Clamp ◽  
Voltage Dependent ◽  
Layer V ◽  
Activity Dependent

Layer V principal neurons of the medial entorhinal cortex receive the main hippocampal output and relay processed information to the neocortex. Despite the fundamental role hypothesized for these neurons in memory replay and consolidation, their dendritic features are largely unknown. High-speed confocal and two-photon Ca2+ imaging coupled with somatic whole cell patch-clamp recordings were used to investigate spike back-propagation in these neurons. The Ca2+ transient associated with a single back-propagating action potential was considerably smaller at distal dendritic locations (>200 μm from the soma) compared with proximal ones. Perfusion of Ba2+ (150 μM) or 4-aminopyridine (2 mM) to block A-type K+ currents significantly increased the amplitude of the distal, but not proximal, Ca2+ transients, which is strong evidence for an increased density of these channels at distal dendritic locations. In addition, the Ca2+ transients decreased with each subsequent spike in a 20-Hz train; this activity-dependent decrease was also more prominent at more distal locations and was attenuated by the perfusion of the protein kinase C activator phorbol-di-acetate. These data are consistent with a phosphorylation-dependent control of back-propagation during trains of action potentials, attributable mainly to an increase in the time constant of recovery from voltage-dependent inactivation of dendritic Na+ channels. In summary, dendritic Na+ and A-type K+ channels control spike back-propagation in layer V entorhinal neurons. Because the activity of these channels is highly modulated, the extent of the dendritic Ca2+ influx is as well, with important functional implications for dendritic integration and associative synaptic plasticity.

Normal Voice Production: Computation of Driving Parameters from Endoscopic Digital High Speed Images

2003 ◽  
Vol 42 (03) ◽  
pp. 271-276 ◽  
Author(s):  
T. Braunschweig ◽  
J. Lohscheller ◽  
U. Eysholdt ◽  
U. Hoppe ◽  
M. Döllinger
Keyword(s):  
Vocal Fold ◽  
High Speed ◽  
Biomechanical Model ◽  
Vocal Folds ◽  
Inversion Algorithm ◽  
Knowledge Based ◽  
Normal Voice ◽  
Inversion Procedure ◽  
High Speed Glottography

Summary Objectives: A central point for quantitative evaluation of pathological and healthy voices is the analysis of vocal fold oscillations. By means of digital High Speed Glottography (HGG), vocal fold oscillations can be recorded in real time. Recently, a numerical inversion procedure was developed that allows the extraction of physiological parameters from digital high speed videos and a classification of voice disorders. The aim of this work was to validate the inversion procedure and to investigate the applicability to normal voices. Methods: High speed recordings were performed during phonation within a group of five female and five male persons with normal voices. By using knowledge based image processing algorithms, motion curves of the vocal folds were extracted at three different positions (dorsal, medial, ventral). These curves were used to obtain physiological voice parameters, and in particular the degree of symmetry of the vocal folds based upon a biomechanical model of the vocal folds. Results: The highest degree of symmetry was observed for the medial motion curves. While the dor-sally and ventrally extracted motion curves exhibited similar results concerning the degree of symmetry the performance of the algorithm was less stable. Conclusions: The inversion algorithm provides reasonable results for all subjects when applied to the medial motion curves. However, for dorsal and ventral motion curves, correct performance is reduced to 85 %.

scholarly journals Three-axis digital holographic microscopy for high speed volumetric imaging

2014 ◽  
Vol 22 (11) ◽  
pp. 13710 ◽  
Author(s):  
F. Saglimbeni ◽  
S. Bianchi ◽  
A. Lepore ◽  
R. Di Leonardo
Keyword(s):  
High Speed ◽  
Digital Holographic Microscopy ◽  
Volumetric Imaging ◽  
Holographic Microscopy
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