Rhythmic Beating Research Articles

Functional Microdomains in Heart's Pacemaker: A Step Beyond Classical Electrophysiology and Remodeling.

Spontaneous beating of the sinoatrial node (SAN), the primary pacemaker of the heart, is initiated, sustained, and regulated by a complex system that integrates ion channels and transporters on the cell membrane surface (often referred to as “membrane clock”) with subcellular calcium handling machinery (by parity of reasoning referred to as an intracellular “Ca2+ clock”). Stable, rhythmic beating of the SAN is ensured by a rigorous synchronization between these two clocks highlighted in the coupled-clock system concept of SAN timekeeping. The emerging results demonstrate that such synchronization of the complex pacemaking machinery at the cellular level depends on tightly regulated spatiotemporal signals which are restricted to precise sub-cellular microdomains and associated with discrete clusters of different ion channels, transporters, and regulatory receptors. It has recently become evident that within the microdomains, various proteins form an interacting network and work together as a part of a macromolecular signaling complex. These protein–protein interactions are tightly controlled and regulated by a variety of neurohormonal signaling pathways and the diversity of cellular responses achieved with a limited pool of second messengers is made possible through the organization of essential signal components in particular microdomains. In this review, we highlight the emerging understanding of the functionality of distinct subcellular microdomains in SAN myocytes and their functional role in the accumulation and neurohormonal regulation of proteins involved in cardiac pacemaking. We also demonstrate how changes in scaffolding proteins may lead to microdomain-targeted remodeling and regulation of pacemaker proteins contributing to SAN dysfunction.

The roles of a flagellar HSP40 ensuring rhythmic beating.

HSP40s are regarded as cochaperones, perpetually shuttling client polypeptides to HSP70s for refolding. However, many HSP40s that are central for disparate processes diverge from this paradigm. To elucidate the noncanonical mechanisms, we investigated HSP40 in the radial spoke (RS) complex in flagella. Disruption of the gene by the MRC1 transposon in Chlamydomonas resulted in jerky flagella. Traditional electron microscopy, cryo-electron tomography, and sub-tomogram analysis revealed RSs of various altered morphologies that, unexpectedly, differed between the two RS species. This indicates that HSP40 locks the RS into a functionally rigid conformation, facilitating its interactions with the adjacent central pair apparatus for transducing locally varied mechanical feedback, which permits rhythmic beating. Missing HSP40, like missing RSs, could be restored in a tip-to-base direction when HSP40 mutants fused with a HSP40 donor cell. However, without concomitant de novo RS assembly, the repair was exceedingly slow, suggesting HSP40/RS-coupled intraflagellar trafficking and assembly. Biochemical analysis and modeling uncovered spoke HSP40’s cochaperone traits. On the basis of our data, we propose that HSP40 accompanies its client RS precursor when traveling to the flagellar tip. Upon arrival, both refold in concert to assemble into the mature configuration. HSP40’s roles in chaperoning and structural maintenance shed new light on its versatility and flagellar biology.

Sinus or not: a new beat detection algorithm based on a pulse morphology quality index to extract normal sinus rhythm beats from wrist-worn photoplethysmography recordings

Objective: Wrist-worn photoplethysmography (PPG) can enable free-living physiological monitoring of people during diverse activities, ranging from sleep to physical exercise. In many applications, it is important to remove the pulses not related to sinus rhythm beats from the PPG signal before using it as a cardiovascular descriptor. In this manuscript, we propose an algorithm to assess the morphology of the PPG signal in order to reject non-sinus rhythm pulses, such as artefacts or pulses related to arrhythmic beats. Approach: The algorithm segments the PPG signal into individual pulses and dynamically evaluates their morphological likelihood of being normal sinus rhythm pulses via a template-matching approach that accounts for the physiological variability of the signal. The normal sinus rhythm likelihood of each pulse is expressed as a quality index that can be employed to reject artefacts and pulses related to arrhythmic beats. Main results: Thresholding the pulse quality index enables near-perfect detection of normal sinus rhythm beats by rejecting most of the non-sinus rhythm pulses (positive predictive value 98%–99%), both in healthy subjects and arrhythmic patients. The rejection of arrhythmic beats is almost complete (sensitivity to arrhythmic beats 7%–3%), while the sensitivity to sinus rhythm beats is not compromised (96%–91%). Significance: The developed algorithm consistently detects normal sinus rhythm beats in a PPG signal by rejecting artefacts and, as a first of its kind, arrhythmic beats. This increases the reliability in the extraction of features which are adversely influenced by the presence of non-sinus pulses, whether related to inter-beat intervals or to pulse morphology, from wrist-worn PPG signals recorded in free-living conditions.

A1668 Expression of miR-139–3p in apoptotic neonatal rat cardiomyocytes induced by hypoxia

Objectives: Myocardial cell apoptosis plays a key role in the development of heart failure. Compared with normal myocardial cells, the hypertrophy myocardial cell apoptosis rate increased significantly, as well as their sensitivity to apoptosis stimulating factor, it may be one of the main cause of heart failure. Recent studies have confirmed that mir-139 -3p is involved in the pathological process of tumor occurrence and development. However, it is not clear about the expression and mechanism of mir-139 -3p in cardiac myocytes. In the present study of our team, the increased expression of mir-139 -3p in the myocardial tissue of hypertensive rats was first detected. In this study, we aim to investigate the expression and clinical significance of miR-139-3p in apoptotic cardiomyocytes induced by hypoxia. Methods: The primary neonatal rat cardiomyocytes were cultured. The cardiomyocytes apoptosis model was established by hypoxia. The expression of caspase-3 in apoptosis model was detected by western-blot. The expression of miR-139-3p was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Results: Myocardial cells were observed pseudopod extend, most of cells appear spontaneous rhythmic beat after 48 h cultured. Compared with the normal control group (0.38 + 0.01), the expression of apoptotic protein caspase-3 (1.01 + 0.02) was significantly increased in the experimental group (P < 0.05). The qRT-PCR analysis demonstrated that both apoptotic cardiomyocytes (Hypoxia group) and normal cardiomyocytes (Control group) expressed miR-139-3p. Moreover, relative expression level of miR-139-3p in Hypoxia group (3.25 ± 0.77) was significantly higher than that in Control group (P < 0.05). Conclusion: Expression of miR-139-3p is significantly higher in apoptotic cardiomyocytes than in normal cardiomyocytes, indica

Neural convergence of rhythm and language: From trait to state

As a growing literature has shed light on associations between cognitive mechanisms for music and language, an important role of rhythm and timing is emerging for individual differences in language skills in children. In this talk we will address: A) how musical rhythm relates to individual differences in spoken grammar traits in children ages 5 to 8; and B) potential neural synchronization by which an overlap in processing rhythm and language might occur. Results in the current study show strong correlations between musical rhythm perception and spoken grammar production, converging with prior work. In addition, we found that individual differences in neural synchronization to the speech envelope (measured with EEG) during passive listening are associated with performance on prosodic and musical rhythm behavioral task performance. Additional EEG data (during musical rhythm beat perception) has also been collected from N = 50 children with typical language development and N = 13 children with grammatical impairments (all children had non-verbal IQ in the normal range); data analysis is underway. In light of these studies and others showing that rhythmic listening can impact grammatical task performance, we will discuss other ongoing translational work that takes first steps towards exploring a causal influence of rhythm on grammar states.

Rhythmic auditory stimulation for gait training in persons with unilateral transtibial amputation: A randomized-controlled trial

The objective of the study is to compare the time taken for prosthetic training using rhythmic auditory stimulation with that of conventional therapy, for unilateral transtibial amputee patients. We will also compare the gait parameters in unilateral transtibial amputee patients trained with and without rhythmic auditory stimulation. Design: randomized-controlled trial with two groups - RAS group and control group. Setting: outpatient and inpatient rehabilitation units, department of PMR, CMC, Vellore. Participants: 29 unilateral transtibial amputee patients ready for prosthetic training, 13 in the RAS group, 16 in the control group (age range 18–65 years). Intervention: rhythmic beats introduced through MP3 players and earphones during prosthetic training for one hour daily. Main outcome measures: the primary outcome measures - included time to complete training, timed up and go (TUG) test and 6 minute walk test (6MWT). The secondary outcome measures were gait velocity, gait cadence, step length, stride length, symmetry, and Physiological Cost Index (PCI). Time required to complete training was 6.08 hours in RAS group and 7.44 hours in the conventional group ( P = 0.159). The mean TUG was 11.09 s in RAS group and 13.43 s in control group ( P -value 0.061). The mean 6MWT was 323.37 m in RAS and 288.96 m in control group ( P -value 0.390). On sub-analysis with exclusion of two skewed variables, statistical significance was found for the TUG test ( P -value 0.020). Step length was found to be better for those in the control group ( P = 0.016 on amputated side and 0.019 on normal side) probably because of external cueing possibly leading to “forced gait” in RAS patients. RAS may potentially decrease the time to completion of training in patients with transtibial amputation. Its effect on improving walking endurance and enabling independent community ambulation for unilateral transtibial amputee patients needs further research with larger studies.

Groove in drum patterns as a function of both rhythmic properties and listeners' attitudes.

Music psychology defines groove as humans’ pleasureable urge to move their body in synchrony with music. Past research has found that rhythmic syncopation, event density, beat salience, and rhythmic variability are positively associated with groove. This exploratory study investigates the groove effect of 248 reconstructed drum patterns from different popular music styles (pop, rock, funk, heavy metal, rock’n’roll, hip hop, soul, R&B). It aims at identifying factors that might be relevant for groove and worth investigating in a controlled setting in the future. Drum patterns of eight bars duration, chosen from 248 popular music tracks, have been transcribed and audio reconstructions have been created on the basis of sound samples. During an online listening experiment, 665 participants rated the reconstructions a total of 8,329 times using a groove questionnaire. Results show that, among 15 tested variables, syncopation (R2 = 0.010) and event density (R2 = 0.011) were positively associated with the groove ratings. These effects were stronger in participants who were music professionals, compared to amateur musicians or mere listeners. A categorisation of the stimuli according to structural aspects was also associated with groove (R2 = 0.018). Beat salience, residual microtiming and rhythmic variability showed no effect on the groove ratings. Participants’ familiarity with a drum pattern had a positive influence on the groove ratings (η2 = 0.051). The largest isolated effect was measured for participants’ style bias (R2 = 0.123): groove ratings tended to be high if participants had the impression that the drum pattern belonged to a style they liked. Combined, the effects of style bias and familiarity (R2 = 0.152) exceeded the other effects as predictors for groove by a wide margin. We conclude that listeners’ taste, musical biographies and expertise have a strong effect on their groove experience. This motivates groove research not to focus on the music alone, but to take the listeners into account as well.

Self-adaptive signal separation for non-contact heart rate estimation from facial video in realistic environments

Objective: Recent research indicates that facial epidermis color varies with the rhythm of heat beats. It can be captured by consumer-level cameras and, astonishingly, be adopted to estimate heart rate (HR). The HR estimated remains not as precise as required in a practical environment where illumination interference, facial expressions, or motion artifacts are involved, although numerous methods have been proposed in the last few years. A novel algorithm is proposed to make non-contact HR estimation technique more robust. Approach: First, the face of the subject is detected and tracked to follow the head movement. The facial region then falls into several blocks, and the chrominance feature of each block is extracted to establish a raw HR sub-signal. Self-adaptive signal separation is performed to separate the noiseless HR sub-signals from raw sub-signals. On that basis, the noiseless sub-signals full of HR information are selected using a weight-based scheme to establish the holistic HR signal, from which the average HR is computed adopting wavelet transform and data filtering. Main results: Forty subjects took part in our experiments, whose facial videos were recorded by a normal webcam with the frame rate of 30 fps under ambient lighting conditions. The average HR estimated by our method correlates strongly with ground truth measurements, as indicated in experimental results measured in a static scenario with the Pearson correlation r = 0.980 and a dynamic scenario with the Pearson correlation r = 0.897. In addition, our method, compared to the newest method, decreases the error rate by 38.63% and increases the Pearson correlation by 15.59%. Significance: This work proposes a robust method for non-contact HR measurement in a realistic environment. Results of comparative experiments indicate that our method out-performs state-of-the-art non-contact HR estimation methods in realistic environments.

Protein⁻Protein Interactions with Connexin 43: Regulation and Function.

Connexins are integral membrane building blocks that form gap junctions, enabling direct cytoplasmic exchange of ions and low-molecular-mass metabolites between adjacent cells. In the heart, gap junctions mediate the propagation of cardiac action potentials and the maintenance of a regular beating rhythm. A number of connexin interacting proteins have been described and are known gap junction regulators either through direct effects (e.g., kinases) or the formation of larger multifunctional complexes (e.g., cytoskeleton scaffold proteins). Most connexin partners can be categorized as either proteins promoting coupling by stimulating forward trafficking and channel opening or inhibiting coupling by inducing channel closure, internalization, and degradation. While some interactions have only been implied through co-localization using immunohistochemistry, others have been confirmed by biophysical methods that allow detection of a direct interaction. Our understanding of these interactions is, by far, most well developed for connexin 43 (Cx43) and the scope of this review is to summarize our current knowledge of their functional and regulatory roles. The significance of these interactions is further exemplified by demonstrating their importance at the intercalated disc, a major hub for Cx43 regulation and Cx43 mediated effects.

Short-Term Effects of Binaural Beats on EEG Power, Functional Connectivity, Cognition, Gait and Anxiety in Parkinson's Disease.

We applied rhythmic binaural sound to Parkinson's Disease (PD) patients to investigate its influence on several symptoms of this disease and on Electrophysiology (Electrocardiography and Electroencephalography (EEG)). We conducted a double-blind, randomized controlled study in which rhythmic binaural beats and control were administered over two randomized and counterbalanced sessions (within-subjects repeated-measures design). Patients ([Formula: see text], age [Formula: see text], stage I-III Hoehn & Yahr scale) participated in two sessions of sound stimulation for 10[Formula: see text]min separated by a minimum of 7 days. Data were collected immediately before and after both stimulations with the following results: (1) a decrease in theta activity, (2) a general decrease in Functional Connectivity (FC), and (3) an improvement in working memory performance. However, no significant changes were identified in the gait performance, heart rate or anxiety level of the patients. With regard to the control stimulation, we did not identify significant changes in the variables analyzed. The use of binaural-rhythm stimulation for PD, as designed in this study, seems to be an effective, portable, inexpensive and noninvasive method to modulate brain activity. This influence on brain activity did not induce changes in anxiety or gait parameters; however, it resulted in a normalization of EEG power (altered in PD), normalization of brain FC (also altered in PD) and working memory improvement (a normalizing effect). In summary, we consider that sound, particularly binaural-rhythmic sound, may be a co-assistant tool in the treatment of PD, however more research is needed to consider the use of this type of stimulation as an effective therapy.

Mitochondrial Dysfunctions Contribute to Hypertrophic Cardiomyopathy in Patient iPSC-Derived Cardiomyocytes with MT-RNR2 Mutation.

SummaryHypertrophic cardiomyopathy (HCM) is the most common cause of sudden cardiac death in young individuals. A potential role of mtDNA mutations in HCM is known. However, the underlying molecular mechanisms linking mtDNA mutations to HCM remain poorly understood due to lack of cell and animal models. Here, we generated induced pluripotent stem cell-derived cardiomyocytes (HCM-iPSC-CMs) from human patients in a maternally inherited HCM family who carry the m.2336T>C mutation in the mitochondrial 16S rRNA gene (MT-RNR2). The results showed that the m.2336T>C mutation resulted in mitochondrial dysfunctions and ultrastructure defects by decreasing the stability of 16S rRNA, which led to reduced levels of mitochondrial proteins. The ATP/ADP ratio and mitochondrial membrane potential were also reduced, thereby elevating the intracellular Ca2+ concentration, which was associated with numerous HCM-specific electrophysiological abnormalities. Our findings therefore provide an innovative insight into the pathogenesis of maternally inherited HCM.

The comparison of clinical and cardiopulmonary effects of xylazine, medetomidine and detomidine in dogs

This study intended to evaluate the effects of α2-adrenoceptor agonists (xylazine, medetomidine and detomidine) on clinical status and cardiopulmonary system in dogs. A total of 30 dogs were randomly assigned to 3 different groups. Following fasting period of 12 hours, xylazine (1 mg/kg IM), medetomidine (25 µ/kg IM) and detomidine (20 µg/kg IM) were administered to groups I, II and III, respectively. Body temperature, heart rates, and respiratory rates were recorded at predetermined times before and after injections. Serum electrolyte, biochemical parameters, blood gases were also evaluated in the blood samples before and after injection. ECG was recorded before, during and after sedation. Decrease in heart rate was found significant in all of the groups. Decrease in the respiration rate was statistically significant (P<0.001) for groups I and II, but not for group III. The decrease in body temperature was statistically significant (P<0.01) only in medetomidine group. Regarding to the biochemical parameters, the increase in blood glucose level was only statistically significant (P<0.05) in group I. Bradycardia, sinoatrial block, 2 Mobitz Type I, and 20 Mobitz Type II block were observed in all groups according to the ECG. Only in medetomidine group, heart rhythm disorders such as escape beat and escape rhythm were observed

Nitric oxide-mediated intersegmental modulation of cycle frequency in the crayfish swimmeret system.

ABSTRACTCrayfish swimmerets are paired appendages located on the ventral side of each abdominal segment that show rhythmic beating during forward swimming produced by central pattern generators in most abdominal segments. For animals with multiple body segments and limbs, intersegmental coordination of central pattern generators in each segment is crucial for the production of effective movements. Here we develop a novel pharmacological approach to analyse intersegmental modulation of swimmeret rhythm by selectively elevating nitric oxide levels and reducing them with pharmacological agents, in specific ganglia. Bath application of L-arginine, the substrate NO synthesis, increased the cyclical spike responses of the power-stroke motor neurons. By contrast the NOS inhibitor, L-NAME decreased them. To determine the role of the different local centres in producing and controlling the swimmeret rhythm, these two drugs were applied locally to two separate ganglia following bath application of carbachol. Results revealed that there was both ascending and descending intersegmental modulation of cycle frequency of the swimmeret rhythm in the abdominal ganglia and that synchrony of cyclical activity between segments of segments was maintained. We also found that there were gradients in the strength effectiveness in modulation, that ascending modulation of the swimmeret rhythm was stronger than descending modulation.

Community effect of cardiomyocytes in beating rhythms is determined by stable cells

The community effect of cardiomyocytes was investigated in silico by the change in number and features of cells, as well as configurations of networks. The theoretical model was based on experimental data and accurately reproduced recently published experimental results regarding coupled cultured cardiomyocytes. We showed that the synchronised beating of two coupled cells was tuned not to the cell with a faster beating rate, but to the cell with a more stable rhythm. In a network of cardiomyocytes, a cell with low fluctuation, but not a hight frequency, became a pacemaker and stabilised the beating rhythm. Fluctuation in beating rapidly decreased with an increase in the number of cells (N), almost irrespective of the configuration of the network, and a cell comes to have natural and stable beating rhythms, even for N of approximately 10. The universality of this community effect lies in the fluctuation-dissipation theorem in statistical mechanics.

Integrate and fire model with refractory period for synchronization of two cardiomyocytes

We investigate an integrate and fire model for two cardiomyocytes interacting with each other. A feature of the model is to incorporate the refractory periods of the cardiomyocytes as well as the influence of firing of adjacent cells. The present model predicts that, if refractory periods of the two cells are nearly equal, the beating rhythms of the two cells always synchronize and their beating rate is tuned to the faster rate between the two cells. On the other hand, if their refractory periods significantly differ, they exhibit various kinds of harmonious beating rhythms. These results successfully explain the well known characteristics of synchronized beating of cultured cardiomyocytes. We also discuss effects of a delay time of cell-to-cell interaction, that gives further complicated phase diagrams for the beating rhythms.

Tool-assisted rhythmic drumming in palm cockatoos shares key elements of human instrumental music.

All human societies have music with a rhythmic "beat," typically produced with percussive instruments such as drums. The set of capacities that allows humans to produce and perceive music appears to be deeply rooted in human biology, but an understanding of its evolutionary origins requires cross-taxa comparisons. We show that drumming by palm cockatoos (Probosciger aterrimus) shares the key rudiments of human instrumental music, including manufacture of a sound tool, performance in a consistent context, regular beat production, repeated components, and individual styles. Over 131 drumming sequences produced by 18 males, the beats occurred at nonrandom, regular intervals, yet individual males differed significantly in the shape parameters describing the distribution of their beat patterns, indicating individual drumming styles. Autocorrelation analyses of the longest drumming sequences further showed that they were highly regular and predictable like human music. These discoveries provide a rare comparative perspective on the evolution of rhythmicity and instrumental music in our own species, and show that a preference for a regular beat can have other origins before being co-opted into group-based music and dance.

On characteristics of Trot singer Bae Ho’s singing voice

In Korea, the trot began shaping its own style in the 1960s. Then, later in the 1970s, it became more specialized having four-fourths beat rhythm of fox-trot, and the Korean style has been finally established with a strong beat and a unique chopping technique. Although there are many trot singers in Korea, the singer Bae Ho was very special in using the heavy bass accompaniment which was later frequently used by other pop singers. The singing voice of Bae Ho gives us the feeling of special softness and appealingness. In addition, his vocalization features the addition of a deep vibe to the song, so that the listeners feel sympathetic and comfortable. This study compares the singing voice of Bae Ho to that of his mimic singers by examining acoustic characteristics of their voices including amplitude, frequency and duration. The acoustic analysis proved that the singing voice of Bae Ho is clearer and has longer duration of vibration in the bass section than that of mimic singers. Bae Ho has a natural talent in expressing the bass part as well as in the midrange part without changing the tone of his voice, while the mimic singers reveal many unnatural connections between measures.

Interactive Rhythm Learning System by Combining Tablet Computers and Robots

This study proposes a percussion learning device that combines tablet computers and robots. This device comprises two systems: a rhythm teaching system, in which users can compose and practice rhythms by using a tablet computer, and a robot performance system. First, teachers compose the rhythm training contents on the tablet computer. Then, the learners practice these percussion exercises by using the tablet computer and a small drum set. The teaching system provides a new and user-friendly score editing interface for composing a rhythm exercise. It also provides a rhythm rating function to facilitate percussion training for children and improve the stability of rhythmic beating. To encourage children to practice percussion exercises, a robotic performance system is used to interact with the children; this system can perform percussion exercises for students to listen to and then help them practice the exercise. This interaction enhances children’s interest and motivation to learn and practice rhythm exercises. The results of experimental course and field trials reveal that the proposed system not only increases students’ interest and efficiency in learning but also helps them in understanding musical rhythms through interaction and composing simple rhythms.

Jonathan Culler. Theory of the Lyric. Cambridge, Mass.: Harvard University Press, 2015. 391pp.

Jonathan Culler. <i>Theory of the Lyric</i>. Cambridge, Mass.: Harvard University Press, 2015. 391pp.

The Relationship and Mechanism Underlying the Effect of Conscious Breathing on the Autonomic Nervous System and Brain Waves

Purpose: Breathing can be controlled either unconsciously or consciously. In Asian countries, various conscious breathing-control techniques have been practiced for many years to promote health and wellbeing. However, the exact mechanism underlying these techniques has not yet been established. The purpose of this study is to explore the physiological mechanism explaining how conscious breathing control could affect the autonomic nervous system, brain activity, and mental changes. Methods: The coupling phenomenon among breathing rhythm, heart rate variability, and brain waves was explored theoretically based on the research hypothesis and a review of the literature. Results: Respiratory sinus arrhythmia is a well-known phenomenon in which heart rate changes to become synchronized with breathing: inhalation increases heart rate and exhalation decreases it. HRV BFB training depends on conscious breathing control. During coherent sinusoidal heart rate changes, brain α waves could be enhanced. An increase in α waves was also found and the synchronicity between heart beat rhythm and brain wave became strengthened during meditation. Conclusion: In addition to the effect of emotion on breathing patterns, conscious breathing could change heart beat rhythms and brainwaves, and subsequently affect emotional status.