One-to-one innervation of vocal muscles allows precise control of birdsong

SummaryThe motor control resolution of any animal behavior is limited to the minimal force step available when activating muscles, which is set by the number and size distribution of motor units (MUs) and muscle specific force [1, 2]. Birdsong is an excellent model system for understanding sequence learning of complex fine motor skills [3], but we know surprisingly little how the motor pool controlling the syrinx is organized [4] and how MU recruitment drives changes in vocal output [5]. Here we combine measurements of syringeal muscle innervation ratios with muscle stress and an in vitro syrinx preparation to estimate MU size distribution and the control resolution of fundamental frequency (fo), a key vocal parameter, in zebra finches. We show that syringeal muscles have extremely small MUs, with 50% innervating ≤ 3, and 13 – 17% innervating a single muscle fiber. Combined with the lowest specific stress (5 mN/mm2) known to skeletal vertebrate muscle, small force steps by the major fo controlling muscle provide control of 50 mHz to 4.2 Hz steps per MU. We show that the song system has the highest motor control resolution possible in the vertebrate nervous system and suggest this evolved due to strong selection on fine gradation of vocal output. Furthermore, we propose that high-resolution motor control was a key feature contributing to the radiation of songbirds that allowed diversification of song and speciation by vocal space expansion.

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Microfluidic device for the formation of optically excitable, three-dimensional, compartmentalized motor units

Science Advances ◽

10.1126/sciadv.1501429 ◽

2016 ◽

Vol 2 (8) ◽

pp. e1501429 ◽

Cited By ~ 96

Author(s):

Sebastien G. M. Uzel ◽

Randall J. Platt ◽

Vidya Subramanian ◽

Taylor M. Pearl ◽

Christopher J. Rowlands ◽

...

Keyword(s):

Motor Neurons ◽

Neuromuscular Junctions ◽

Three Dimensional ◽

Embryonic Stem ◽

Motor Units ◽

Cell Types ◽

In Vitro Assays ◽

Traumatic Injuries ◽

Muscle Innervation

Motor units are the fundamental elements responsible for muscle movement. They are formed by lower motor neurons and their muscle targets, synapsed via neuromuscular junctions (NMJs). The loss of NMJs in neurodegenerative disorders (such as amyotrophic lateral sclerosis or spinal muscle atrophy) or as a result of traumatic injuries affects millions of lives each year. Developing in vitro assays that closely recapitulate the physiology of neuromuscular tissues is crucial to understand the formation and maturation of NMJs, as well as to help unravel the mechanisms leading to their degeneration and repair. We present a microfluidic platform designed to coculture myoblast-derived muscle strips and motor neurons differentiated from mouse embryonic stem cells (ESCs) within a three-dimensional (3D) hydrogel. The device geometry mimics the spinal cord–limb physical separation by compartmentalizing the two cell types, which also facilitates the observation of 3D neurite outgrowth and remote muscle innervation. Moreover, the use of compliant pillars as anchors for muscle strips provides a quantitative functional readout of force generation. Finally, photosensitizing the ESC provides a pool of source cells that can be differentiated into optically excitable motor neurons, allowing for spatiodynamic, versatile, and noninvasive in vitro control of the motor units.

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Formation and Structure of Casein Micelles in Lactating Mammary Tissue

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100067741 ◽

1970 ◽

Vol 28 ◽

pp. 150-151

Author(s):

Robert J. Carroll ◽

Marvin P. Thompson ◽

Harold M. Farrell

Keyword(s):

Size Distribution ◽

G Protein ◽

Milk Proteins ◽

Mammary Tissue ◽

Colloidal System ◽

Casein Micelles ◽

The Stability

Milk is an unusually stable colloidal system; the stability of this system is due primarily to the formation of micelles by the major milk proteins, the caseins. Numerous models for the structure of casein micelles have been proposed; these models have been formulated on the basis of in vitro studies. Synthetic casein micelles (i.e., those formed by mixing the purified αsl- and k-caseins with Ca2+ in appropriate ratios) are dissimilar to those from freshly-drawn milks in (i) size distribution, (ii) ratio of Ca/P, and (iii) solvation (g. water/g. protein). Evidently, in vivo organization of the caseins into the micellar form occurs in-a manner which is not identical to the in vitro mode of formation.

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Pharmacokinetics and Haemostatic Status During Consecutive Infusions of Recom binant Tissue-Type Plasminogen Activator in Patients with Acute Myocardial Infarction

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646622 ◽

1989 ◽

Vol 61 (03) ◽

pp. 497-501 ◽

Cited By ~ 47

Author(s):

E Seifried ◽

P Tanswell ◽

D Ellbrück ◽

W Haerer ◽

A Schmidt

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Plasminogen Activator ◽

Peak Plasma ◽

Peak Plasma Concentration ◽

Tissue Type ◽

Tissue Type Plasminogen Activator ◽

Precise Control ◽

Type Plasminogen Activator

SummaryPharmacokinetics and systemic effects of recombinant tissue type plasminogen activator (rt-PA) were determined during coronary thrombolysis in 12 acute myocardial infarction patients using a consecutive intravenous infusion regimen. Ten mg rt-PA were infused in 2 minutes resulting in a peak plasma concentration (mean ±SD) of 3310±950 ng/ml, followed by 50 mg in 1 h and 30 mg in 1.5 h yielding steady state plasma levels of. 2210±470 nglml and 930±200 ng/ml, respectively. All patients received intravenous heparin. Total clearance of rt-PA was 380±74 ml/min, t,½α was 3.6±0.9 min and t,½β was 16±5.4 min.After 90 min, in plasma samples containing anti-rt-PA-IgG to inhibit in vitro effects, fibrinogen was decreased to 54%, plasminogen to 52%, α2-antiplasmin to 25%, α2-macroglobulin to 90% and antithrombin III to 85% of initial values. Coagulation times were prolonged and fibrin D-dimer concentrations increased from 0.40 to 2.7 μg/ml. It is concluded that pharmacokinetics of rt-PA show low interpatient variability and that its short mean residence time in plasma allows precise control of therapy. Apart from its moderate effect on the haemostatic system, rt-PA appears to lyse a fibrin pool in addition to the coronary thrombus.

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Optimization and Characterization of Aqueous Micellar Formulations for Ocular Delivery of an Antifungal Drug, Posaconazole

Current Pharmaceutical Design ◽

10.2174/1381612826666200313172207 ◽

2020 ◽

Vol 26 (14) ◽

pp. 1543-1555 ◽

Cited By ~ 2

Author(s):

Meltem E. Durgun ◽

Emine Kahraman ◽

Sevgi Güngör ◽

Yıldız Özsoy

Keyword(s):

Particle Size ◽

Zeta Potential ◽

Size Distribution ◽

Encapsulation Efficiency ◽

Fungal Infections ◽

In Vitro Release ◽

Pluronic F127 ◽

Glycol Succinate ◽

Vitro Release

Background: Topical therapy is preferred for the management of ocular fungal infections due to its superiorities which include overcoming potential systemic side effects risk of drugs, and targeting of drugs to the site of disease. However, the optimization of effective ocular formulations has always been a major challenge due to restrictions of ocular barriers and physiological conditions. Posaconazole, an antifungal and highly lipophilic agent with broad-spectrum, has been used topically as off-label in the treatment of ocular fungal infections due to its highly lipophilic character. Micellar carriers have the potential to improve the solubility of lipophilic drugs and, overcome ocular barriers. Objective: In the current study, it was aimed optimization of posaconazole loaded micellar formulations to improve aqueous solubility of posaconazole and to characterize the formulations and to investigate the physical stability of these formulations at room temperature (25°C, 60% RH), and accelerated stability (40°C, 75% RH) conditions. Method: Micelles were prepared using a thin-film hydration method. Pre-formulation studies were firstly performed to optimize polymer/surfactant type and to determine their concentration in the formulations. Then, particle size, size distribution, and zeta potential of the micellar formulations were measured by ZetaSizer Nano-ZS. The drug encapsulation efficiency of the micelles was quantified by HPLC. The morphology of the micelles was depicted by AFM. The stability of optimized micelles was evaluated in terms of particle size, size distribution, zeta potential, drug amount and pH for 180 days. In vitro release studies were performed using Franz diffusion cells. Results: Pre-formulation studies indicated that single D-ɑ-tocopheryl polyethylene glycol succinate (TPGS), a combination of it and Pluronic F127/Pluronic F68 are capable of formation of posaconazole loaded micelles at specific concentrations. Optimized micelles with high encapsulation efficiency were less than 20 nm, approximately neutral, stable, and in aspherical shape. Additionally, in vitro release data showed that the release of posaconazole from the micelles was higher than that of suspension. Conclusion: The results revealed that the optimized micellar formulation of posaconazole offers a potential approach for topical ocular administration.

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In Vitro Human Joint Models Combining Advanced 3D Cell Culture and Cutting-Edge 3D Bioprinting Technologies

Cells ◽

10.3390/cells10030596 ◽

2021 ◽

Vol 10 (3) ◽

pp. 596

Author(s):

Christian Jorgensen ◽

Matthieu Simon

Keyword(s):

New Technology ◽

3D Cell Culture ◽

External Pressure ◽

New Drugs ◽

Cellular Interactions ◽

Joint Models ◽

Physical Stimulation ◽

Precise Control ◽

Diarthrodial Joint

Joint-on-a-chip is a new technology able to replicate the joint functions into microscale systems close to pathophysiological conditions. Recent advances in 3D printing techniques allow the precise control of the architecture of the cellular compartments (including chondrocytes, stromal cells, osteocytes and synoviocytes). These tools integrate fluid circulation, the delivery of growth factors, physical stimulation including oxygen level, external pressure, and mobility. All of these structures must be able to mimic the specific functions of the diarthrodial joint: mobility, biomechanical aspects and cellular interactions. All the elements must be grouped together in space and reorganized in a manner close to the joint organ. This will allow the study of rheumatic disease physiopathology, the development of biomarkers and the screening of new drugs.

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Nanoformulation and Evaluation of Oral Berberine-Loaded Liposomes

Molecules ◽

10.3390/molecules26092591 ◽

2021 ◽

Vol 26 (9) ◽

pp. 2591

Author(s):

Thuan Thi Duong ◽

Antti Isomäki ◽

Urve Paaver ◽

Ivo Laidmäe ◽

Arvo Tõnisoo ◽

...

Keyword(s):

Thin Film ◽

Drug Release ◽

Size Distribution ◽

Water Soluble ◽

Release Behavior ◽

Uniform Size ◽

Ethanol Injection ◽

Drug Release Behavior ◽

Poorly Water Soluble

Berberine (BBR) is a poorly water-soluble quaternary isoquinoline alkaloid of plant origin with potential uses in the drug therapy of hypercholesterolemia. To tackle the limitations associated with the oral therapeutic use of BBR (such as a first-pass metabolism and poor absorption), BBR-loaded liposomes were fabricated by ethanol-injection and thin-film hydration methods. The size and size distribution, polydispersity index (PDI), solid-state properties, entrapment efficiency (EE) and in vitro drug release of liposomes were investigated. The BBR-loaded liposomes prepared by ethanol-injection and thin-film hydration methods presented an average liposome size ranging from 50 nm to 244 nm and from 111 nm to 449 nm, respectively. The PDI values for the liposomes were less than 0.3, suggesting a narrow size distribution. The EE of liposomes ranged from 56% to 92%. Poorly water-soluble BBR was found to accumulate in the bi-layered phospholipid membrane of the liposomes prepared by the thin-film hydration method. The BBR-loaded liposomes generated by both nanofabrication methods presented extended drug release behavior in vitro. In conclusion, both ethanol-injection and thin-film hydration nanofabrication methods are feasible for generating BBR-loaded oral liposomes with a uniform size, high EE and modified drug release behavior in vitro.

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Tuning the network charge of biohybrid hydrogel matrices to modulate the release of SDF-1

Biological Chemistry ◽

10.1515/hsz-2021-0175 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Sebastian Kühn ◽

Joanna Freyse ◽

Passant Atallah ◽

Jörg Rademann ◽

Uwe Freudenberg ◽

...

Keyword(s):

Bone Repair ◽

Negative Charge ◽

Polymer Networks ◽

Signaling Molecules ◽

Treatment Modalities ◽

Precise Control ◽

Integral Density ◽

New Treatment ◽

Two Parameters

Abstract The delivery of chemotactic signaling molecules via customized biomaterials can effectively guide the migration of cells to improve the regeneration of damaged or diseased tissues. Here, we present a novel biohybrid hydrogel system containing two different sulfated glycosaminoglycans (sGAG)/sGAG derivatives, namely either a mixture of short heparin polymers (Hep-Mal) or structurally defined nona-sulfated tetrahyaluronans (9s-HA4-SH), to precisely control the release of charged signaling molecules. The polymer networks are described in terms of their negative charge, i.e. the anionic sulfate groups on the saccharides, using two parameters, the integral density of negative charge and the local charge distribution (clustering) within the network. The modulation of both parameters was shown to govern the release characteristics of the chemotactic signaling molecule SDF-1 and allows for seamless transitions between burst and sustained release conditions as well as the precise control over the total amount of delivered protein. The obtained hydrogels with well-adjusted release profiles effectively promote MSC migration in vitro and emerge as promising candidates for new treatment modalities in the context of bone repair and wound healing.

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Evaluation of Child–Computer Interaction Using Fitts’ Law: A Comparison between a Standard Computer Mouse and a Head Mouse

Sensors ◽

10.3390/s21113826 ◽

2021 ◽

Vol 21 (11) ◽

pp. 3826

Author(s):

Cristina Sanchez ◽

Vanina Costa ◽

Rodrigo Garcia-Carmona ◽

Eloy Urendes ◽

Javier Tejedor ◽

...

Keyword(s):

Motor Control ◽

Inertial Sensor ◽

Psychomotor Development ◽

Fine Motor ◽

Input Devices ◽

Fitts Law ◽

Computer Mouse ◽

Adults And Children ◽

Study Participants ◽

Computer Interaction

This study evaluates and compares the suitability for child–computer interaction (CCI, the branch within human–computer interaction focused on interactive computer systems for children) of two devices: a standard computer mouse and the ENLAZA interface, a head mouse that measures the user’s head posture using an inertial sensor. A multidirectional pointing task was used to assess the motor performance and the users’ ability to learn such a task. The evaluation was based on the interpretation of the metrics derived from Fitts’ law. Ten children aged between 6 and 8 participated in this study. Participants performed a series of pre- and post-training tests for both input devices. After the experiments, data were analyzed and statistically compared. The results show that Fitts’ law can be used to detect changes in the learning process and assess the level of psychomotor development (by comparing the performance of adults and children). In addition, meaningful differences between the fine motor control (hand) and the gross motor control (head) were found by comparing the results of the interaction using the two devices. These findings suggest that Fitts’ law metrics offer a reliable and objective way of measuring the progress of physical training or therapy.

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