Rhythmic Beating Research Articles

Electrical Remodeling in Fibrillating Canine Atrium Action Potential Alternans During Rapid Atrial Pacing and Late Phase 3 Early Afterdepolarization After Cessation of Rapid Atrial Pacing

Sustained atrial fibrillation (AF) was induced by atrial burst pacing, and monophasic action potentials (MAPs) were recorded. MAP alternans was observed at a cycle length (CL) of 167.5 ± 28.2 msec before burst pacing and 201.3 ± 40.2 msec after burst pacing. AF > 5 minutes duration was induced in 1 dog in the control condition but in all 8 dogs after burst pacing. The difference in RA MAPD(80) of the first spontaneous beat and steady-state sinus rhythm was significantly larger after atrial burst pacing than before atrial burst pacing (31.5 ± 15.9 msec versus 8.2 ± 9.0 msec) In 4 dogs, late phase 3 early after depolarization was observed after rapid atrial pacing. Rapid atrial pacing-induced electrical remodeling includes APD alternans during rapid atrial pacing and also causes an increase in the MAPD of the initial several beats and the development of late phase 3 early afterdepolarizations after a sudden increase in CL.

Mechanism of the Spontaneous Beating of Skeletal-Based Precursor of Cardiomyocytes (SPOC)

The skeletal muscle-based precursor of cardiomyocytes (SPOC), a stem cell that potentially differentiates into heart cells [Winitsky et al. (2005) PloS Biol 3(4), e87], were isolated from leg skeletal muscle of the rat. Initially the SPOC cells had round and small appearance. When cultured on the dishes coated with extracellular matrix, they differentiated into round, tear drop, or tubular shaped cells. During the course of their differentiation, the SPOC cells exhibited a rhythmic beating associated with spontaneous oscillation of the intracellular Ca2+. The spontaneous beating could be suppressed by Cd2+ and nifedipine, indicating possible contribution of the L-type Ca2+-channel to the development of the automaticity. The rate of the spontaneous beating was accelerated by the administration of isoproterenol. Immunocytochemistry of the SPOC cells indicated the existence of Nkx 2.5, cardiac TnT, dihydropyridine receptor, and ryanodine receptor. Action potentials during the spontaneous beating and the underlying membrane currents were analyzed by using the patch-clamp technique. Our results indicate that the SPOC cells develop their automaticity by a unique mechanism distinct from that of skeletal or heart muscle cells.

Development of Novel System for the Functional Analysis of the Cardiomyocytes Network Model Using On-Chip Cellomics Technology

Spatial and temporal regulation of cellular orientation is one of the key to resolve the mechanism of organs and tissues that are complexly intertwined with epigenetic factors, such as cellular network size and orientation of cellular-type. To study the dynamics of synchronous beating rhythm in the cardiac myocytes, we tried to develop the agarose micro-chamber (AMC) system on the multi-electrode array (MEA) chip, and extra-cellular signals of cardiomyocytes in geometrically patterning chambers were recorded with On-Chip MEA system. The chip set consists with the type of MEA chip, pattern of AMC and cellular-type, for example, primary mouse embryonic, ES and iPS derived cardiomyocyts. By using the cell handling by micropipette and additional fabrication to the AMC during the cultivation, we are able to construct the normal and disordered model. For example, we made the loop structure as reentry model having length of the circuit above the millimeter. Under this system, it is possible to obtain a multiple of information about individual cell (as constitutional unit) and entire network (as organ model) by field potential recordings (FPs) and optical imaging. Pseudo-ECG, which sum the FPs obtained from each electrode, means whole network signal and duration time of pseudo-ECG corresponds to QT interval. From analysis of individual FPs, direction of the excitement propagation and conduction velocity is resolved. Waveform analysis of FPs give us the relative intensity of Na+, Ca2+ and K+ currents and field potential duration (FPD) corresponding to action potential duration (APD). On-Chip geometric re-constitutive approaches are powerful tools for stepwise cell network construction and long-term measurement of it, and also will make possible the development of the novel system for the toxicity studies of drugs.

영어 기능어 연쇄 발화의 리듬구조

This study attempts to investigate rhythmic patterns and structures in function word sequences of English. In the phonetic experiment, we examined five different lengths and three different types of sequences varying with the neighboring word construction. The intervals between two pitch accents in the string of function words were measured in terms of the number of syllables to see the extent to which a rhythmic beat stretches in English. In addition, a priority ordering of pitch accent assignment among function words was explored and compared with the one suggested by Giegerich (1968). Results show that the maximum number of unstressed syllables was varied depending on the length and the types of function word sequences, one to seven, but that the maximum number of lapsed words as opposed to syllables was consistently three. As prosodic prominence is manifested as a pitch accent at the level of utterance in English, it is contented that unaccented words as opposed to unstressed syllable should be counted as the weak counterpart within a rhythmic unit. Moreover, it is suggested that this rhythmic unit construing in the postlexical level should be called ‘accentual foot,’ following Lee & Kang (2009) and that it should be distinctive from ‘foot’ at the lexical level. Similar to the lexical foot that a stressed syllable can be followed by maximally two unstressed ones, the accentual foot is generally composed of one accented word followed by maximally three accented words. The ordering of accented function words is, in general, consistent with that of Giegerich (1968) in that modal verbs are most likely to be accented, and that auxiliaries are the least. What should be noticed in the ordering results was that phrase final pronouns were rarely accented and should deserve to be considered as a separate category because they cause a change in the whole rhythmic pattern of a sentence.

Heart of the Beat (the Flagellar Beat, that Is)

Heart of the Beat (the Flagellar Beat, that Is)

The Role of the Basal Ganglia in Beat Perception

Perception of musical rhythms is culturally universal. Despite this special status, relatively little is known about the neurobiology of rhythm perception, particularly with respect to beat processing. Findings are presented here from a series of studies that have specifically examined the neural basis of beat perception, using functional magnetic resonance imaging (fMRI) and studying patients with Parkinson's disease. fMRI data indicate that novel beat-based sequences robustly activate the basal ganglia when compared to irregular, nonbeat sequences. Furthermore, although most healthy participants find it much easier to discriminate changes in beat-based sequences compared to irregular sequences, Parkinson's disease patients fail to show the same degree of benefit. Taken together, these data suggest that the basal ganglia are performing a crucial function in beat processing. The results of an additional fMRI study indicate that the role of the basal ganglia is strongly linked to internal generation of the beat. Basal ganglia activity is greater when participants listen to rhythms in which internal generation of the beat is required, as opposed to rhythms with strongly externally cued beats. Functional connectivity between part of the basal ganglia (the putamen) and cortical motor areas (premotor and supplementary motor areas) is also higher during perception of beat rhythms compared to nonbeat rhythms. Increased connectivity between cortical motor and auditory areas is found in those with musical training. The findings from these converging methods strongly implicate the basal ganglia in processing a regular beat, particularly when internal generation of the beat is required.

Analysis of 126 patients with atrial fibrillation complicating long R-R Interval by Dynamic Elec-trocardiogram

Objective To analyze the relationship between atrial fibrillation complicating long R-R interval, escape beat and escape heart rhythm and pathological atrioventricular block by dynamic electrocardiography (DCG). Methods 126 patients with atrial fibrillation were divided into group A (being related to sleep) and group B (being not related to sleep) according to the factor whether long R-R interval, escape beat and escape heart rhythm relevant to sleep. All were detected by DCG for 24 hours. Results The cases with1.5～2.0 s long R-R interval, more than 2.0s long R-R interval, escape beat and escape heart rhythm were (26.02±6.03), (7.39±1.05 ) and (6.90±1.28)in group A and (203.05±41.01), (35.48±7.52), (28.10±6.25) in group B respectively. The cases of group B were markedly more than those in group A. Conclusion Those atrial fibrillation complicating long R-R interval, escape bbeat and escape heart rhythm were related to sleep could not be deemed as pathological atrioventricular block, while those were not related to sleep could be considered pathological atrioventricular block. Key words: Dynamic electrocardiogram; Atrial fibrillation; Long R-R interval; Atrioventricular block

Feeling the Beat: Premotor and Striatal Interactions in Musicians and Nonmusicians during Beat Perception

Little is known about the underlying neurobiology of rhythm and beat perception, despite its universal cultural importance. Here we used functional magnetic resonance imaging to study rhythm perception in musicians and nonmusicians. Three conditions varied in the degree to which external reinforcement versus internal generation of the beat was required. The "volume" condition strongly externally marked the beat with volume changes, the "duration" condition marked the beat with weaker accents arising from duration changes, and the "unaccented" condition required the beat to be entirely internally generated. In all conditions, beat rhythms compared with nonbeat control rhythms revealed putamen activity. The presence of a beat was also associated with greater connectivity between the putamen and the supplementary motor area (SMA), the premotor cortex (PMC), and auditory cortex. In contrast, the type of accent within the beat conditions modulated the coupling between premotor and auditory cortex, with greater modulation for musicians than nonmusicians. Importantly, the response of the putamen to beat conditions was not attributable to differences in temporal complexity between the three rhythm conditions. We propose that a cortico-subcortical network including the putamen, SMA, and PMC is engaged for the analysis of temporal sequences and prediction or generation of putative beats, especially under conditions that may require internal generation of the beat. The importance of this system for auditory-motor interaction and development of precisely timed movement is suggested here by its facilitation in musicians.

Rhythmic structures in content word untterances.

This study investigates rhythmic structures in the utterances composed of only content words. Content words are potentially accentable in utterance, and English necessitates a rhythmic alternation between strong and weak beats. What will happen if only content words are sequenced and they are all one‐syllable words? A phonetic experiment was conducted to see if a rhythmic pattern is still produced in content word utterances and how it is manifested along the intonational contours. Results showed that merely 7% of the utterances were produced with every content word accented. Most utterances were rhythmically produced with every two (38%) or three (26%) words accented, and the other patterns such as a H* and L* alternation, two H*’s intervened with L‐, and consecutive downstepped H*’s were interpreted as conforming the tonal rhythm [J.‐K. Lee and S. Kang, Korean J. Speech Sci., 10(2), 303–317 (2003)]. In two‐syllable content word utterances, the patterns where two words were unaccented suggest that strong and weak rhythmic beats should be counted with the number of words rather than syllables at the level of utterance. It is proposed that it is an accentual foot as opposed to a lexical foot at the level of lexical word.

Connexin 43 expression is impaired in beginning heart failure in spontaneously hypertensive rats

Arrhythmia is a severe problem in many pathological conditions of the heart such as cardiomyopathy and heart failure. As gap junctions provide the basis for a regular rhythmic beating and regular electrical propagation, connexins forming gap junctions in the heart have been very attractive targets for scientific research in the past. While in hypertrophy Cx43 is up-regulated, in heart failure Cx43 has been shown to be decreased. We therefore wanted to elucidate whether spontaneously hypertensive rats showing signs of impaired ventricular function have altered Cx43 levels and if so, which pathways are involved in these changes.

C-kit expression identifies cardiovascular precursors in the neonatal heart

Directed differentiation of embryonic stem cells indicates that mesodermal lineages in the mammalian heart (cardiac, endothelial, and smooth muscle cells) develop from a common, multipotent cardiovascular precursor. To isolate and characterize the lineage potential of a resident pool of cardiovascular progenitor cells (CPcs), we developed BAC transgenic mice in which enhanced green fluorescent protein (EGFP) is placed under control of the c-kit locus (c-kit(BAC)-EGFP mice). Discrete c-kit-EGFP(+) cells were observed at different stages of differentiation in embryonic hearts, increasing in number to a maximum at about postnatal day (PN) 2; thereafter, EGFP(+) cells declined and were rarely observed in the adult heart. EGFP(+) cells purified from PN 0-5 hearts were nestin(+) and expanded in culture; 67% of cells were fluorescent after 9 days. Purified cells differentiated into endothelial, cardiac, and smooth muscle cells, and differentiation could be directed by specific growth factors. CPc-derived cardiac myocytes displayed rhythmic beating and action potentials characteristic of multiple cardiac cell types, similar to ES cell-derived cardiomyocytes. Single-cell dilution studies confirmed the potential of individual CPcs to form all 3 cardiovascular lineages. In adult hearts, cryoablation resulted in c-kit-EGFP(+) expression, peaking 7 days postcryolesion. Expression occurred in endothelial and smooth muscle cells in the revascularizing infarct, and in terminally differentiated cardiomyocytes in the border zone surrounding the infarct. Thus, c-kit expression marks CPc in the neonatal heart that are capable of directed differentiation in vitro; however, c-kit expression in cardiomyocytes in the adult heart after injury does not identify cardiac myogenesis.

Elastic Matrices that mimic normal heart are best for beating Cardiomyocytes - Beating stops on mechanical mimics of Scars

Fibrotic rigidification following a myocardial infarct is known to impair cardiac output, and it is also known that cardiomyocytes on rigid culture substrates show a progressive loss of rhythmic beating. Here, isolated embryonic cardiomyocytes cultured on a series of flexible substrates show that matrices which mimic the elasticity of the developing myocardial microenvironment are optimal for transmitting contractile work to the matrix and for promoting actomyosin striation and 1 Hz beating. On hard matrices that mechanically mimic a post-infarct fibrotic scar, cells over-strain themselves, lack striated myofibrils and stop beating; on very soft matrices, cells preserve contractile beating for days in culture but do very little work. Optimal matrix leads to a strain match between cell and matrix and suggests dynamic differences in intracellular protein structures. A “Cysteine Shotgun” method of labeling the in situ proteome reveals differences in assembly or conformation of several abundant cytoskeletal proteins, including vimentin, filamin, and myosin. Combined with recent results that show stem cell differentiation is also highly sensitive to matrix elasticity, the results here highlight the need for greater attention to fibrosis and mechanical microenvironments in cell therapy.

Speech rhythm in Akan oral praise poetry

This article reports a study of harmonic speech displayed in Akan oral praise poetry (apae). The study demonstrates that the recitation of Akan praise poetry—a fairly free verse form in terms of variable tempo and line length—is highly influenced by an isochronous rhythmic beat. Despite isolated occurrences of relatively long or short non-isochronous metrical accents, these poems are recited in a style that exploits tempo changes and ellipsis to maintain an oscillatory rhythm of beats at harmonic intervals, and this rhythm is found to remain constant through silent rest phases between individual poems as well as between lines. This research supports the notion that considerations of timing should be given more weight in linguistic theory and modeling.

Serum response factor orchestrates nascent sarcomerogenesis and silences the biomineralization gene program in the heart

Our conditional serum response factor (SRF) knockout, Srf (Cko), in the heart-forming region blocked the appearance of rhythmic beating myocytes, one of the earliest cardiac defects caused by the ablation of a cardiac-enriched transcription factor. The appearance of Hand1 and Smyd1, transcription and chromatin remodeling factors; Acta1, Acta2, Myl3, and Myom1, myofibril proteins; and calcium-activated potassium-channel gene activity (KCNMB1), the channel protein, were powerfully attenuated in the Srf(CKO) mutant hearts. A requisite role for combinatorial cofactor interactions with SRF, as a major determinant for regulating the appearance of organized sarcomeres, was shown by viral rescue of SRF-null ES cells with SRF point mutants that block cofactor interactions. In the absence of SRF genes associated with biomineralization, GATA-6, bone morphogenetic protein 4 (BMP4), and periostin were strongly up-regulated, coinciding with the down regulation of many SRF dependent microRNA, including miR1, which exerted robust silencer activity over the induction of GATA-6 leading to the down regulation of BMP4 and periostin.

Foxj1 transcription factors are master regulators of the motile ciliogenic program

Motile cilia induce fluid movement through their rhythmic beating activity. In mammals, the transcription factor Foxj1 has been implicated in motile cilia formation. Here we show that a zebrafish Foxj1 homolog, foxj1a, is a target of Hedgehog signaling in the floor plate. Loss of Foxj1a compromises the assembly of motile cilia that decorate floor plate cells. Besides the floor plate, foxj1a is expressed in Kupffer's vesicle and pronephric ducts, where it also promotes ciliary differentiation. We show that Foxj1a activates a constellation of genes essential for motile cilia formation and function, and that its activity is sufficient for ectopic development of cilia that resemble motile cilia. We also document that a paralogous gene, foxj1b, is expressed in the otic vesicle and seems to regulate motile cilia formation in this tissue. Our findings identify a dedicated master regulatory role for Foxj1 in the transcriptional program that controls the production of motile cilia.

Embryonic cardiomyocytes beat best on a matrix with heart-like elasticity: scar-like rigidity inhibits beating

Fibrotic rigidification following a myocardial infarct is known to impair cardiac output, and it is also known that cardiomyocytes on rigid culture substrates show a progressive loss of rhythmic beating. Here, isolated embryonic cardiomyocytes cultured on a series of flexible substrates show that matrices that mimic the elasticity of the developing myocardial microenvironment are optimal for transmitting contractile work to the matrix and for promoting actomyosin striation and 1-Hz beating. On hard matrices that mechanically mimic a post-infarct fibrotic scar, cells overstrain themselves, lack striated myofibrils and stop beating; on very soft matrices, cells preserve contractile beating for days in culture but do very little work. Optimal matrix leads to a strain match between cell and matrix, and suggests dynamic differences in intracellular protein structures. A 'cysteine shotgun' method of labeling the in situ proteome reveals differences in assembly or conformation of several abundant cytoskeletal proteins, including vimentin, filamin and myosin. Combined with recent results, which show that stem cell differentiation is also highly sensitive to matrix elasticity, the methods and analyses might be useful in the culture and assessment of cardiogenesis of both embryonic stem cells and induced pluripotent stem cells. The results described here also highlight the need for greater attention to fibrosis and mechanical microenvironments in cell therapy and development.

Hydrodynamics of ciliary propulsion

A numerical approach is developed to study the effect on a fluid of the regular oscillations of an array of flexible cilia which hinge around points on a wall. The specific application studied concerns the ctenophore Pleurobrachia pileus, a small marine invertebrate of quasi-spherical shape and diameter of the order of the centimeter which swims in water thanks to the rhythmic beating of eight rows of hair-like cilia aligned along its body. Only one row of cilia is studied here, in a three-dimensional setting. The technique presented is general enough to allow its application to a variety of fluid–structure interaction problems. The physical mechanisms of the propulsion are highlighted, by analysing the results of three-dimensional simulations. A parametric study involving natural and non-natural parameters leads to a better understanding of the propulsive characteristics of ctenophores; results show that the specific power expended increases with the increase of the beating frequency of the row of cilia, in agreement with experiments.

Point:Counterpoint: Respiratory sinus arrhythmia is due to a central mechanism vs. respiratory sinus arrhythmia is due to the baroreflex mechanism

Blood pressure and heart periods fluctuate at respiratory frequencies in healthy humans. Some researchers ([8][1], [23][2]) explain this as a cause-and-effect relation: blood pressure changes trigger baroreflex-mediated R-R interval changes. Here I make the case that respiratory sinus arrhythmia is

Folding at the rhythm of the rare codon beat

The persistent difficulties in the production of protein at high levels in heterologous systems, as well as the inability to understand pathologies associated with protein aggregation, highlight our limited knowledge on the mechanisms of protein folding in vivo. Attempts to improve yield and quality of recombinant proteins are diverse, frequently involving optimization of the cell growth temperature, the use of synonymous codons and/or the co-expression of tRNAs, chaperones and folding catalysts among others. Although protein secondary structure can be determined largely by the amino acid sequence, protein folding within the cell is affected by a range of factors beyond amino acid sequence. The folding pathway of a nascent polypeptide can be affected by transient interactions with other proteins and ligands, the ribosome, translocation through a pore membrane, redox conditions, among others. The translation rate as well as the translation machinery itself can dramatically affect protein folding, and thus the structure and function of the protein product. This review addresses current efforts to better understand how the use of synonymous codons in the mRNA and the availability of tRNAs can modulate translation kinetics, affecting the folding, the structure and the biological activity of proteins.

Predicting n:1 locking in pulse coupled two-neuron networks using phase resetting theory

Background Harmonic locking has been observed between breathing and heart beat rhythms, in hippocampal slices between interneurons firing at gamma and pyramidal neurons firing at beta frequencies with missed gamma beats and in model networks between theta and gamma rhythms. Existence and stability criteria for harmonic locking modes were derived for two reciprocally pulse coupled oscillators based on their first and second order phase resetting curves (PRCs). These methods were then tested using two reciprocally inhibitory Wang and Buzsaki model neurons. Methods PRCs were generated in an open loop configuration and applied to the analysis of the circuit under the assumption that after each perturbation the trajectory returns near its limit cycle and that the synaptic inputs received in the closed loop circuit remain similar to those used to generate the PRCs [1]. Figure 1A shows how an assumed firing pattern can be used to produce a map, which can then be linearized for a stability analysis. The dots indicate a variable number of spikes in the faster neuron 1. The periodicity criteria in this case are ts1 [n] = tr2 [n], ts21 [n] = tr11 [n], ts22 [n] = tr12 [n] with the intervals defined as shown in the figure. The periodicity criteria can be rewritten in from Seventeenth Annual Computational Neuroscience Meeting: CNS*2008 Portland, OR, USA. 19–24 July 2008