Rate Of Contraction Research Articles

TIMP3 induces gene expression partly through PI3K and their association with vascularization and heart rate.

Tissue inhibitor of metalloproteinase 3 (TIMP3) was recently demonstrated capable to regulate some gene expression in a myocardial infarction model. Here we aim to explore the gene expression profile in TIMP3-treated cardiomyocytes and related potential cardiovascular functions. Total RNA extracted from cultured neonatal rat ventricular myocytes (NRVMs) were used for RNA sequencing analysis and real-time PCR. KEGG pathway enrichment assay and Ingenuity Pathway Analysis (IPA) were performed to study the signaling pathways and downstream effects. Western blot was used to detect phosphorylation of protein kinase B (Akt). A Cell Counting Kit-8 assay was employed to evaluate the proliferation of human umbilical vein endothelial cells (HUVECs). Contraction rate of NRVMs was measured with microscopy. RNA sequencing data showed that expression of 2,526 genes were significantly modulated by recombinant TIMP3 (rTIMP3, 100 ng/ml) in NRVMs. Some differentially expressed genes (DEGs) were validated with real-time PCR. Several KEGG pathways including the phosphoinositide-3-kinase (PI3K)-Akt pathway were significantly regulated by rTIMP3. Phosphorylation of Akt was increased by rTIMP3 and a PI3K inhibitor LY294002 suppressed rTIMP3-induced up-regulation of some genes. Some DEGs were predicted by IPA to increase vascularization, and some to decrease heart rate. RTIMP3 could reduce the contraction rate of NRVMs and its conditioned media increased the proliferation of HUVECs. TIMP3 can regulate expression of multiple genes partly through PI3K. Some DEGs were associated with activation of vascularization and some with heart rate reduction. This study suggests that TIMP3 can potentially modulate cardiovascular functions via DEGs.

Metabolomics analysis reveals serum biomarkers in patients with diabetic sarcopenia.

Diabetic sarcopenia (DS) is characterized by muscle atrophy, slower nerve conduction, reduced maximum tension generated by skeletal muscle contraction, and slower contraction rate. Hence, DS can cause limb movement degeneration, slow movement, reduced balance, reduced metabolic rate, falls, fractures, etc. Moreover, the relevant early biological metabolites and their pathophysiological mechanism have yet to be characterized. The current cross-sectional study employed serum metabolomics analysis to screen potential noninvasive biomarkers in patients with diabetic sarcopenia. A total of 280 diabetic patients were enrolled in the study (n = 39 sarcopenia [DS], n = 241 without sarcopenia [DM]). Ten patients were randomly selected from both groups. Non-targeted metabolomic analysis was performed by ultra-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry. A total of 632 differential metabolites were identified, including 82 that were significantly differentially abundant (P < 0.05, VIP > 1, FC > 1.2 or FC < 0.8). Compared with the DM group, the contents of pentadecanoic acid, 5'-methylthioadenosine (5'-MTA), N,N-dimethylarginine (asymmetric dimethylarginine, ADMA), and glutamine in the DS group were significantly increased, while that of isoxanthohumol was decreased. Based on receiver operating characteristic curve analysis, pentadecanoic acid, 5'-MTA, ADMA, and glutamine may serve as potential biomarkers of DS. Moreover, ATP-binding cassette (ABC) transporters and the mammalian target of the rapamycin signaling pathway were found to potentially have important regulatory roles in the occurrence and development of DS (P < 0.05). Collectively, the differential metabolites identified in this study provide new insights into the underlying pathophysiology of DS and serve as a basis for therapeutic interventions.

Wound Healing Activity of Cotton Fabrics Loaded with Silver Nanoparticles in Experimental Model of Diabetes

Diabetes is connected with diminished wound healing, that makes patients liable to continuing difficult wounds. Metal nanomaterials as single conjugates have established to keep possible properties of wound when metal nanoparticles are coupled with other wound covering materials. This study aimed to investigate a possible role of cotton fabrics full with silver nanoparticles (AgNPs) to enhance wound healing in diabetic model induced by streptozotocin (STZ).Animals were classified into four groups including the wounded group that were equivalently covered with sterile dressing that made of cotton fabric which had been saturated with different concentrations of silver nanoparticles, and the control group that was preserved with only cotton covering without any treatment (blank group); percent of wound contraction in different studied groups was estimated. Plasma nitric oxide (NO), malodialdehyde (MDA), reduced glutathione (GSH) were measured. Serum neutrophil elastase and nuclear factor kappa b (NF-κb) were assayed by ELISA. Homocystiene (Hcy) was estimated by HPLC. Our results revealed an elevation in wound area, MDA, NF-κb, Hcy, and elastase in the wound group compared to treated groups concomitant with a decrease in plasma nitric oxide and reduced glutathione activities, while treatment with AgNPs significantly ameliorated these parameters in treated group compared to blank group. AgNPs showed high wound contraction rates according to their used concentration .In conclusion; AgNPs have gained considerable attention amongst researchers in wound healing applications, owing to their physicochemical and biological properties. AgNPs promote wound healing and effectively control the growth of microorganisms at the wound site, and this strategy plays an important role in the treatment of wounds.

Evaluation of the Wound Healing Potential of Hypericum triquetrifolium Turra: An Experimental Animal Study and Histopathological Examination

The wound healing potential of the aerial parts of Hypericum triquetrifolium Turra (Hypericaceae) was evaluated using an in vivo excision wound model in rats. Adult male Sprague Dawley rats were randomly assigned into seven groups; blank vehicles (olive oil and petroleum jelly), negative control, treatments [H. triquetrifolium ethanolic extract in petroleum jelly (5% and 10%) and H. triquetrifolium olive oil macerate (100 and 200 g/L)], and positive control (MEBO). Treatments were applied topically once daily until the wounds had completely healed. Wound areas and contraction rates were calculated, and full-thickness samples of the healed skin were collected for histopathological examination. H. triquetrifolium ointment (5%) showed the best wound healing activity with statistically significant differences when compared with the MEBO, petroleum jelly, and the negative control groups. Tissue sections were histopathologically examined in terms of re-epithelialization, granulation tissue development, collagen deposition, inflammatory cell infiltration, angiogenesis, and ulcer formation to support the in vivo excision wound model findings. H. triquetrifolium ointment (5%) showed the best histopathological scores in both re-epithelialization and ulcer formation. For quality control purposes, a high-performance liquid chromatography (HPLC) method was used to quantify key marker compounds in the extract, namely hypericin and rutin which showed a content of 0.64% and 4.46% (w/w), respectively. Based on the experimental results, H. triquetrifolium ointment (5%) exhibits remarkable wound healing properties at various stages of the wound healing process. Further investigations to prove its safety and efficacy in different types of wounds and to uncover its cellular mechanisms are warranted.

Intelligent antepartum fetal monitoring via deep learning and fusion of cardiotocographic signals and clinical data.

Cardiotocography (CTG), which measures uterine contraction (UC) and fetal heart rate (FHR), is a crucial tool for assessing fetal health during pregnancy. However, traditional computerized cardiotocography (cCTG) approaches have non-negligible calibration errors in feature extraction and heavily rely on the expertise and prior experience to define diagnostic features from CTG or FHR signals. Although previous works have studied deep learning methods for extracting CTG or FHR features, these methods still neglect the clinical information of pregnant women. In this paper, we proposed a multimodal deep learning architecture (MMDLA) for intelligent antepartum fetal monitoring that is capable of performing automatic CTG feature extraction, fusion with clinical data and classification. The multimodal feature fusion was achieved by concatenating high-level CTG features, which were extracted from preprocessed CTG signals via a convolution neural network (CNN) with six convolution layers and five fully connected layers, and the clinical data of pregnant women. Eventually, light gradient boosting machine (LGBM) was implemented as fetal status assessment classifier. The effectiveness of MMDLA was evaluated using a dataset of 16,355 cases, each of which includes FHR signal, UC signal and pertinent clinical data like maternal age and gestational age. With an accuracy of 90.77% and an area under the curve (AUC) value of 0.9201, the multimodal features performed admirably. The data imbalance issue was also effectively resolved by the LGBM classifier, with a normal-F1 value of 0.9376 and an abnormal-F1 value of 0.8223. In summary, the proposed MMDLA is conducive to the realization of intelligent antepartum fetal monitoring.

Fixed-Domain Posterior Contraction Rates for Spatial Gaussian Process Model with Nugget

Spatial Gaussian process regression models typically contain finite dimensional covariance parameters that need to be estimated from the data. We study the Bayesian estimation of covariance parameters including the nugget parameter in a general class of stationary covariance functions under fixed-domain asymptotics, which is theoretically challenging due to the increasingly strong dependence among spatial observations. We propose a novel adaptation of the Schwartz’s consistency theorem for showing posterior contraction rates of the covariance parameters including the nugget. We derive a new polynomial evidence lower bound, and propose consistent higher-order quadratic variation estimators that satisfy concentration inequalities with exponentially small tails. Our Bayesian fixed-domain asymptotics theory leads to explicit posterior contraction rates for the microergodic and nugget parameters in the isotropic Matérn covariance function under a general stratified sampling design. We verify our theory and the Bayesian predictive performance in simulation studies and an application to sea surface temperature data. Supplementary materials for this article are available online.

Owl-Neck-Spine-Inspired, Additively Manufactured, Joint Assemblies with Shape Memory Alloy Wire Actuators.

Nature provides a considerable number of good examples for simple and very efficient joint assemblies. One example is the enormously flexible cervical spine of American barn owls, which consists of 14 cervical vertebrae. Each pair of vertebrae produces a comparatively small individual movement in order to provide a large overall movement of the entire cervical spine. The biomimetic replication of such joints is difficult due to the delicate and geometric unrestricted joint shapes as well as the muscles that have to be mimicked. Using X-ray as well as micro-computed tomography images and with the utilisation of additive manufacturing, it was possible to produce the owl neck vertebrae in scaled-up form, to analyse them and then to transfer them into technically usable joint assemblies. The muscle substitution of these joints was realised by smart materials actuators in the form of shape memory alloy wire actuators. This actuator technology is outstanding for its muscle-like movement and for its high-energy density. The disadvantage of this wire actuator technology is the low rate of contraction, which means that a large length of wire has to be installed to generate adequate movement. For this reason, the actuator wires were integrated into additively manufactured carrier components to mimic biological joints. This resulted in joint designs that compensate for the disadvantages of the small contraction of the actuators by intelligently installing large wire lengths on comparatively small installation spaces, while also providing a sufficient force output. With the help of a test rig, the developed technical joint variants are examined and evaluated. This demonstrated the technical applicability of this biomimetic joints.

Holocene right-lateral slip-rate revealed by sediment core analyses and ground penetrating radar profiling, the Sagiriko fault, Izu Peninsula, Japan, at the northern tip of the Izu–Bonin–Mariana arc

On the Izu Peninsula of Japan, the Sagiriko fault group is located to the south of the Kita-Izu fault zone, which ruptured during the 1930 Kita-Izu earthquake (Mjma = 7.3). A NS-trending strand of the Sagiriko fault group was ruptured during the 1930 earthquake, but conjugate EW-trending strands were not ruptured, and no Holocene activity on them has been documented. We surveyed the near-surface structure across the Sagiriko-b fault, one of the EW-trending strands, by ground penetrating radar profiling and radiocarbon dating of sediments obtained from two drilling cores. The results revealed a right-lateral displacement of 5.5 m of fluvial terraces around the survey site that formed after about 10 ka. The right-lateral slip-rate was calculated to be more than 0.55 mm/yr. This rate, which is significantly smaller than the crustal contraction rate in this area, suggests that the crustal contraction was probably spread across several EW-trending active faults parallel to the Sagiriko-b fault.

Effect of cold atmospheric plasma/NO gas application with different exposure times on healing in wounds with tissue loss in diabetic rats.

Applications of cold atmospheric plasma/nitric oxide (CAP/NO) gas have recently garnered popularity when treating impaired wound healing in patients with diabetes. In this study, we aimed to investigate the effects of NO gas application for 60 and 120 s on wound healing in diabetic rats. A dorsal excision 3 cm in diameter was performed in 15 diabetic rats; these rats were categorized into the following 3 groups: DC (untreated diabetic control); DNO/60 (exposure to 200 ppm NO gas for 60 s/day); and DNO/120 (exposure to 200 ppm NO gas for 120 s/day). Wound contraction on days 0, 3, 7, 11, and 14 and wound contraction rate between days 0 and 14 were evaluated. On day 14, tissue samples were collected for histopathologic assessment of inflammation, epithelial regeneration, angiogenesis congestion, and collagen fiber organization. Normality of distribution was assessed using the Shapiro-Wilk test, and intergroup comparisons were performed using the Mann-Whitney U test (NPar Test) and the Kruskal-Wallis test (non-parametric ANOVA). Wound contraction during treatment days 7-14 was significantly greater in the NO-treatment groups than in the DC group (p<0.05). The NO60 s and NO120 s groups showed a significantly higher wound contraction rate than the DC group (p=0.033, p=0.049, respectively). Significant differences were noted between the control and NO groups in terms of inflammation (p<0.05) and between the control group and DNO/60 and DNO/120 groups in terms of collagen organization (p<0.05, p<0.01, respectively). Evaluation of epithelialization revealed significant intergroup differences between the control and NO treatment groups (p<0.01). In this study, the application of NO once a day for 60 seconds and 120 seconds in diabetic wounds contributed equally to wound healing.

In vivo healing potential of Vitis Vinifera L. and Punica Granatum L. fruit extracts in excision and burn models in rabbits

Abstract Aim. The present study was carried out to evaluate the wound healing potential of crude Hydroalcoholic fruit extracts of Grape (Vitis vinifera L.) and Pomegranate (Punica granatum L.) in experimental animals. Material and methods. Extracts were formulated as ointments (250 mg), and their wound healing properties were determined by using two models: i.e. excision and burn models, in rabbits. Wound healing potential was assessed by measuring rate of wound contraction (percentage wound contraction) and the epithelialization period. Tukey test (HSD) test was used to analyze the obtained results. The value of p &lt;0.05 was considered as a level of significance. The reference standard was wadded Cicatryl® ointment. Results. The result showed that crude fruit extracts of Vitis vinifera L. and Punica granatum L. exhibited a significant (p &lt;0.0001) rate of wound contraction and significant (p&lt;0.0001) decrease in the period of epithelialization compared to the control (untreated) group in both the models studied. Conclusion. Our results suggest that topical treatment of fruit extracts of Vitis vinifera L. and Punica granatum L. accelerate wound healing activity, thus our study supports their traditional use. Both extracts can be used as a potential source of wound healing therapeutics.

First steps towards modeling the interaction of cardiovascular agents and smooth muscle activation in arterial walls

AbstractNumerical simulation of the response of healthy and pathological arteries to cardiovascular agents can provide valuable information to the physician in the treatment of diseases such as hypertension, atherosclerosis, and the Marfan syndrome. Here, we provide a first step towards a computational framework to model the effects of antihypertensive agents on the mechanical response of arterial walls. A material model is developed by extending an existing formulation for wall tissue to incorporate the effects of calcium‐ion channel blockers. The resulting coupled deformation‐diffusion problem is then solved using the finite element method. Simulation results with drug activity show that, indeed, an increased lumen diameter due to reduced contraction is obtained. Additionally, a decrease in the rate of arterial contraction is observed, which is also consistent with expected behavior. Finally, we compare results for an implicit or explicit treatment of the the deformation‐diffusion coupling, and we observe that both coupling schemes yield comparable results for a wide range of time step sizes.

Persistent Unilateral Force Production Deficits Following Hand Injury in Experienced Climbers: A Reliability and Retrospective Injury Study.

In climbing, research is needed to guide clinical and training advice regarding strength differences between hands. The objectives of this study were to establish test-retest reliability of a field-based apparatus measuring sport-specific unilateral isometric hand strength and to investigate whether these measures detect between-hand differences in climbers with and without a history of unilateral hand injury. A reliability and case-control injury study was carried out. Seventeen intermediate-advanced climbers without and 15 intermediate-advanced climbers with previous unilateral hand injury participated. Unilateral isometric fingertip flexor strength was assessed during maximal voluntary contraction (MVC) and peak rate of force development (RFD) tests in full-crimp overhead position. The magnitude of within-group between-hand differences was calculated using a generalized estimating equation to evaluate if prior injury was associated with lower MVC and RFD outcomes and whether hand dominance influenced the magnitude of these effects. The control group was assessed 1 wk later to determine intraclass correlation coefficients (ICCs) for all measures. The MVC (ICC 0.91-0.93) and the RFD (ICC 0.92-0.83) tests demonstrated moderate-to-high reliability. When accounting for handedness, those with prior injury showed 7% (P=0.004) reduced MVC and 13% (P=0.008) reduced RFD in the injured hand. The nondominant hand was also significantly weaker in MVC (11%, P<0.001) and RFD (12%, P=0.02) outcomes. For uninjured climbers, MVC and RFD were not significantly higher in the dominant hand (differing by 4% and 5%, respectively). Previous climbing injury was associated with persistent weakness in the injured limb and exacerbated handedness effects. Therefore, recommendations for rehabilitation should be considered.

Scalable Bayesian High-dimensional Local Dependence Learning

In this work, we propose a scalable Bayesian procedure for learning the local dependence structure in a high-dimensional model where the variables possess a natural ordering. The ordering of variables can be indexed by time, the vicinities of spatial locations, and so on, with the natural assumption that variables far apart tend to have weak correlations. Applications of such models abound in a variety of fields such as finance, genome associations analysis and spatial modeling. We adopt a flexible framework under which each variable is dependent on its neighbors or predecessors, and the neighborhood size can vary for each variable. It is of great interest to reveal this local dependence structure by estimating the covariance or precision matrix while yielding a consistent estimate of the varying neighborhood size for each variable. The existing literature on banded covariance matrix estimation, which assumes a fixed bandwidth cannot be adapted for this general setup. We employ the modified Cholesky decomposition for the precision matrix and design a flexible prior for this model through appropriate priors on the neighborhood sizes and Cholesky factors. The posterior contraction rates of the Cholesky factor are derived which are nearly or exactly minimax optimal, and our procedure leads to consistent estimates of the neighborhood size for all the variables. Another appealing feature of our procedure is its scalability to models with large numbers of variables due to efficient posterior inference without resorting to MCMC algorithms. Numerical comparisons are carried out with competitive methods, and applications are considered for some real datasets.

Transmission risk of COVID-19 infection with office-based flexible laryngoscopy

Since the beginning of the Coronavirus pandemic, recommendations to ensure safety in clinical practice have fluctuated. Within the Otolaryngology community, a variety of protocols have emerged to assure safety for both patients and healthcare workers while maintaining standard of care practices, especially surrounding aerosolizing in-office procedures. ObjectivesThis study aims to describe our Otolaryngology Department's Personal Protective Equipment protocol for both patients and providers during office laryngoscopy and to identify the risk of contracting COVID-19 after implementation of the protocol. Methods18,953 office visits divided between 2019 and 2020 where laryngoscopy was performed were examined and compared to the rate of COVID-19 contraction for both office staff and patients within a 14 day period after the encounter. Of these visits, two cases were examined and discussed; where a patient tested positive for COVID-19 ten days after office laryngoscopy, and one where a patient tested positive for COVID-19 ten days prior to office laryngoscopy. ResultsIn the year 2020, 8337 office laryngoscopies were performed, 100 patients tested positive within the year 2020, with only these 2 cases of COVID-19 infections occurring within 14 days prior to or after their office visit. ConclusionThese data suggest that using CDC-compliant protocol for aerosolizing procedures, such as office laryngoscopy, can provide a safe and effective method for mitigating infectious risk while providing timely quality care for the otolaryngology patient. Level of evidence3 Lay summaryDuring the COVID-19 Pandemic, ENTs have had to balance providing care while minimizing the risk of COVID-19 transmission with routine office procedures such as flexible laryngoscopy. In this large chart review, we show that the risk of transmission is low with CDC-compliant protective equipment and cleaning protocols.

Madder (Rubia cordifolia L.) Alleviates Myocardial Ischemia-Reperfusion Injury by Protecting Endothelial Cells from Apoptosis and Inflammation.

Ischemia-reperfusion injury often occurs in organ transplantation, coronary heart disease, ischemic heart disease, and other diseases, which greatly reduces clinical efficacy. This study examined the effectiveness of madder as a medicine to treat ischemia-reperfusion injury. The efficacy of madder was evaluated by measuring myocardial infarction size, coronary outflow volume, myocardial contraction rate, activation of inflammatory factors, autophagy factors, apoptosis factors, and related pathway genes in mice. The results indicated that treatment with madder can effectively reduce the area of myocardial infarction and restore arterial blood flow velocity and myocardial contractility in mice. Additionally, madder treatment inhibited the expression of inflammatory factors, autophagy factors, and apoptosis factors in mice and reduced the degree of myocardial cell injury. Studies have also shown that madder treatment can alleviate myocardial ischemia-reperfusion injury in mice and inhibit the occurrence of inflammatory response by inhibiting the activity of the NF-κB pathway. The results showed that madder was effective against ischemia-reperfusion injury, thus showing potential as a clinical drug for treating ischemia-reperfusion injury.

Voluntary torque production is unaffected by changes in local thermal sensation during normothermia and hyperthermia.

What is the central question of this study? Hyperthermia reduces the human capacity to produce muscular force, which is associated with decreased neural drive: does mitigating a reduction in neural drive by altering localised thermal sensation help to preserve voluntary force output? What is the main finding and its importance? Altering thermal sensation by cooling and heating the head independent of core temperature did not change neural drive or benefit voluntary force production. Head cooling did slow the rate of rise in core temperature during heating, which may have practical applications in passive settings. This study investigated altered local head and neck thermal sensation on maximal and rapid torque production during voluntary contractions. Nine participants completed four visits in two environmental conditions: at rectal temperatures ∼39.5°C in hot (HOT; ∼50°C, ∼39% relative humidity) and ∼37°C in thermoneutral (NEU; ∼22°C, ∼46% relative humidity) conditions. Local thermal sensation was manipulated by heating in thermoneutral conditions and cooling in hot conditions. Evoked twitches and octets were delivered at rest. Maximum voluntary torque (MVT), normalised surface electromyography (EMG) and voluntary activation (VA) were assessed during brief maximal isometric voluntary contractions of the knee extensors. Rate of torque development (RTD) and EMG were measured during rapid voluntary contractions. MVT (P=0.463) and RTD (P=0.061) were similar between environmental conditions despite reduced VA (-6%; P=0.047) and EMG at MVT (-31%; P=0.019). EMG in the rapid voluntary contractions was also lower in HOT versus NEU during the initial 100ms (-24%; P=0.035) and 150ms (-26%; P=0.035). Evoked twitch (+70%; P<0.001) and octet (+27%; P<0.001) RTD during the initial 50ms were greater in the HOT compared to NEU conditions, in addition to a faster relaxation rate of the muscle (-33%; P<0.001). In conclusion, hyperthermia reduced neural drive without affecting voluntary torque, likely due to the compensatory effects of improved intrinsic contractile function and faster contraction and relaxation rates of the knee extensors. Changes in local thermal perception of the head and neck whilst hyperthermic or normothermic did not affect voluntary torque.

The Study of the Wrinkles of Hexagonal Boron-Nitride Flake after the Annealing

Hexagonal boron nitride (h-BN) flakes have been widely used due to their excellent physical and chemical properties. Here, thermal-induced wrinkles of thin h-BN flakes deposited on silicon dioxide substrate were investigated through a combination of atomic force microscopy (AFM) and Raman spectroscopy. The experimental results indicated that the wrinkles did not occur at relatively low annealing temperatures and were detected at temperatures as high as 500 °C or even 600 °C. When repeatedly annealed at high temperatures, the number and positions of the wrinkles also changed. From the Raman spectra, the wrinkles were caused by the fact that the h-BN contraction rate was faster than that of the substrate at the cooling stage due to the interfacial sliding between the flake and the substrate and the h-BN flake of 7 nm thickness recovered to the original length at 150 °C. Further cooling introduced the compressive stress and then the wrinkles appeared. Moreover, it was found that if there was a crack in the h-BN flake, the wrinkle always appeared at the crack. Our findings appeal the mechanism of thermal-induced wrinkles of h-BN flakes and help us to research their applications as substrate materials in electronic devices in a high-temperature environment.

Motor processivity and speed determine structure and dynamics of microtubule-motor assemblies.

Active matter systems can generate highly ordered structures, avoiding equilibrium through the consumption of energy by individual constituents. How the microscopic parameters that characterize the active agents are translated to the observed mesoscopic properties of the assembly has remained an open question. These active systems are prevalent in living matter; for example, in cells, the cytoskeleton is organized into structures such as the mitotic spindle through the coordinated activity of many motor proteins walking along microtubules. Here, we investigate how the microscopic motor-microtubule interactions affect the coherent structures formed in a reconstituted motor-microtubule system. This question is of deeper evolutionary significance as we suspect motor and microtubule type contribute to the shape and size of resulting structures. We explore key parameters experimentally and theoretically, using a variety of motors with different speeds, processivities, and directionalities. We demonstrate that aster size depends on the motor used to create the aster, and develop a model for the distribution of motors and microtubules in steady-state asters that depends on parameters related to motor speed and processivity. Further, we show that network contraction rates scale linearly with the single-motor speed in quasi-one-dimensional contraction experiments. In all, this theoretical and experimental work helps elucidate how microscopic motor properties are translated to the much larger scale of collective motor-microtubule assemblies.

Optical modulation of excitation-contraction coupling in human-induced pluripotent stem cell-derived cardiomyocytes

Non-genetic photostimulation is a novel and rapidly growing multidisciplinary field that aims to induce light-sensitivity in living systems by exploiting exogeneous phototransducers. Here, we propose an intramembrane photoswitch, based on an azobenzene derivative (Ziapin2), for optical pacing of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The light-mediated stimulation process has been studied by applying several techniques to detect the effect on the cell properties. In particular, we recorded changes in membrane capacitance, in membrane potential (Vm), and modulation of intracellular Ca2+ dynamics. Finally, cell contractility was analyzed using a custom MATLAB algorithm. Photostimulation of intramembrane Ziapin2 causes a transient Vm hyperpolarization followed by a delayed depolarization and action potential firing. The observed initial electrical modulation nicely correlates with changes in Ca2+ dynamics and contraction rate. This work represents the proof of principle that Ziapin2 can modulate electrical activity and contractility in hiPSC-CMs, opening up a future development in cardiac physiology.

An amphiphilic plasma membrane-targeted photo-transducer mediates optical pacing in cardiomyocytes derived from human induced pluripotent stem cells.

The use of light to control the activity of different cell-types has recently come at the forefront of the scientific community thanks to a series of key-enabling characteristics (i.e. spatial/temporal selectivity, and lower invasiveness). Notably, non-genetic photostimulation is a novel and rapidly growing multidisciplinary field of research that aims to induce light sensitivity in living systems by exploiting exogeneous phototransducers. Here we propose a recently synthetized actuator, based on an azobenzene derivative, for cardiac applications. The light-mediated photostimulation process has been studied by applying several characterization techniques to detect the effect on the cellular properties of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). In particular, we recorded changes in membrane capacitance, in membrane potential (Vm), intracellular Ca2+ dynamics and cell contractility. Light stimulation of the photo-transducers causes a transient Vm hyperpolarization followed by a delayed depolarization and action potential (AP) generation. The observed increase in AP frequency nicely correlates with changes in Ca2+ dynamics and contraction rate. Altogether, these preliminrary evidences provide the proof of concept that our amphiphilic plasma membrane-targeted photo-transducer is a viable tool to modulate electrical activity and contractility in hiPSC-CMs, opening up a broader field of applications in cardiac electrophysiology.