Axonemal Symmetry Break, a New Ultrastructural Diagnostic Tool for Primary Ciliary Dyskinesia?

Diagnosis testing for primary ciliary dyskinesia (PCD) requires a combination of investigations that includes study of ciliary beat pattern by high-speed video-microscopy, genetic testing and assessment of the ciliary ultrastructure by transmission electron microscopy (TEM). Historically, TEM was considered to be the “gold standard” for the diagnosis of PCD. However, with the advances in molecular genetic techniques, an increasing number of PCD variants show normal ultrastructure and cannot be diagnosed by TEM. During ultrastructural assessment of ciliary biopsies of patients with suspicion of PCD, we observed an axonemal defect not previously described that affects peripheral doublets tilting. To further characterize this defect of unknown significance, we studied the ciliary axonemes by TEM from both PCD-confirmed patients and patients with other sino-pulmonary diseases. We detected peripheral doublets tilting in all the PCD patients, without any significant difference in the distribution of ciliary beat pattern or mutated gene. This defect was also present in those patients with normal ultrastructure PCD subtypes. We believe that the performance of axonemal asymmetry analysis would be helpful to enhance diagnosis of PCD.

Beat Patterns Determine Inter-Hand Differences in Synchronization Error in a Bimanual Coordination Tapping Task

A previous study reported the unique finding that people tapping a beat pattern with the right hand produce larger negative synchronization error than when tapping with the left hand or other effectors, in contrast to previous studies that have shown that the hands tap patterns simultaneously without any synchronization errors. We examined whether the inter-hand difference in synchronization error occurred due to handedness or to a specificity of the beat pattern employed in that study. Two experiments manipulated the hand–beat assignments. A comparison between the identical beat to the pacing signal and a beat with a longer interval excluded the handedness hypothesis and demonstrated that beat patterns with relatively shorter intervals were tapped earlier (Experiment 1). These synchronization errors were not local but occurred consistently throughout the beat patterns. Experiment 2 excluded alternative explanations. These results indicate that the apparent inconsistency in previous studies was due to the specificity of the beat patterns, suggesting that a beat pattern with a relatively shorter interval between hands is tapped earlier than beats with longer intervals. Our finding that the bimanual tapping of different beat patterns produced different synchronization errors suggests that the notion of a central timing system may need to be revised.

Reconstruction of the three-dimensional beat pattern underlying swimming behaviors of sperm

The eukaryotic flagellum propels sperm cells and simultaneously detects physical and chemical cues that modulate the waveform of the flagellar beat. Most previous studies have characterized the flagellar beat and swimming trajectories in two space dimensions (2D) at a water/glass interface. Here, using refined holographic imaging methods, we report high-quality recordings of three-dimensional (3D) flagellar bending waves. As predicted by theory, we observed that an asymmetric and planar flagellar beat results in a circular swimming path, whereas a symmetric and non-planar flagellar beat results in a twisted-ribbon swimming path. During swimming in 3D, human sperm flagella exhibit torsion waves characterized by maxima at the low curvature regions of the flagellar wave. We suggest that these torsion waves are common in nature and that they are an intrinsic property of beating axonemes. We discuss how 3D beat patterns result in twisted-ribbon swimming paths. This study provides new insight into the axoneme dynamics, the 3D flagellar beat, and the resulting swimming behavior. Graphic abstract

Multi-ciliated microswimmers–metachronal coordination and helical swimming

The dynamics and motion of multi-ciliated microswimmers with a spherical body and a small number N (with $$5< N < 60$$ 5 < N < 60 ) of cilia with length comparable to the body radius, is investigated by mesoscale hydrodynamics simulations. A metachronal wave is imposed for the cilia beat, for which the wave vector has both a longitudinal and a latitudinal component. The dynamics and motion is characterized by the swimming velocity, its variation over the beat cycle, the spinning velocity around the main body axis, as well as the parameters of the helical trajectory. Our simulation results show that the microswimmer motion strongly depends on the latitudinal wave number and the longitudinal phase lag. The microswimmers are found to swim smoothly and usually spin around their own axis. Chirality of the metachronal beat pattern generically generates helical trajectories. In most cases, the helices are thin and stretched, i.e., the helix radius is about an order of magnitude smaller than the pitch. The rotational diffusion of the microswimmer is significantly smaller than the passive rotational diffusion of the body alone, which indicates that the extended cilia contribute strongly to the hydrodynamic radius. The swimming velocity is found to increase with the cilia number N with a slightly sublinear power law, consistent with the behavior expected from the dependence of the transport velocity of planar cilia arrays on the cilia separation. Graphic abstract

A tail’s tale: Biomechanical roles of dorsal thoracic spine of barnacle nauplii

Many marine invertebrates have complex life histories that begin with a planktonic larval stage. Similar to other plankton, these larval invertebrates often possess protruding body extensions, but their function beyond predator deterrence is not well-documented. For example, the planktonic nauplii of crustaceans have spines. Using the epibiotic pedunculate barnacle Octolasmis spp., we investigated how the dorsal thoracic spine affects swimming and fluid disturbance by comparing nauplii with their spines partially removed against those with intact spines. Our motion analysis showed that amputated Octolasmis spp. swam slower, in jerkier trajectories, and were less efficient per stroke cycle than those with intact spines. Amputees showed alterations in limb beat pattern: larger beat amplitude, increased phase lag, and reduced contralateral symmetry. These changes might partially help increase propulsive force generation and streamline the flow, but were insufficient to restore full function. Particle image velocimetry further showed that amputees had a larger relative area of influence, implying elevated risk by rheotactic predator. Body extensions and their interactions with limb motion play important biomechanical roles in shaping larval performance, which likely influences the evolution of form.

A new kind of beat

New mathematical model reveals how the flagella of some single-celled algae generate a lasso-like beat pattern that propels the cell through water.

Beat patterns determine inter-hand differences in synchronization error in a bimanual coordination tapping task.

A previous study reported the unique finding that people tap a beat pattern with the right hand earlier than with the left hand or other effectors, in contrast to previous studies that have shown that the hands tap patterns simultaneously without any synchronization errors. We examined whether the inter-hand difference in synchronization error occurred due to handedness or to a specificity of the beat pattern employed in that study. Two experiments manipulated the hand–beat assignments. A comparison between the identical beat to the pacing signal and a beat with a longer interval excluded the handedness hypothesis and demonstrated that beat patterns with relatively shorter intervals were tapped earlier (Experiment 1). These synchronization errors were not local but occurred consistently throughout the beat patterns. Experiment 2 excluded alternative explanations. These results indicate that the apparent inconsistency in previous studies was due to the specificity of the beat patterns, suggesting that a beat pattern with a shorter interval is tapped earlier than beats with longer intervals. Our results are consistent with a model of central timing control in bimanual tapping.

A minimal robophysical model of quadriflagellate self-propulsion

Locomotion at the microscale is remarkably sophisticated. Microorganisms have evolved diverse strategies to move within highly viscous environments, using deformable, propulsion-generating appendages such as cilia and flagella to drive helical or undulatory motion. In single-celled algae, these appendages can be arranged in different ways around an approximately 10µm cell body, and coordinated in distinct temporal patterns. Inspired by the observation that some quadriflagellates (bearing four flagella) have an outwardly similar morphology and flagellar beat pattern, yet swim at different speeds, this study seeks to determine whether variations in swimming performance could arise solely from differences in swimming gait. Robotics approaches are particularly suited to such investigations, where the phase relationships between appendages can be readily manipulated. Here, we developed autonomous, algae-inspired robophysical models that can self-propel in a viscous fluid. These macroscopic robots (length and width = 8.5 cm, height = 2 cm) have four independently actuated ‘flagella’ that oscillate back and forth under low-Reynolds number conditions (Re∼ 𝒪(10−1)). We tested the swimming performance of these robot models with appendages arranged in one of two distinct configurations, and coordinated in one of three distinct gaits. The gaits, namely the pronk, the trot, and the gallop, correspond to gaits adopted by distinct microalgal species. When the appendages are inserted perpendicularly around a central ‘body’, the robot achieved a net performance of 0.15−0.63 body lengths per cycle, with the trot gait being the fastest. Robotic swimming performance was found to be comparable to that of the algal microswimmers across all gaits. By creating a minimal robot that can successfully reproduce cilia-inspired drag-based swimming, our work paves the way for the design of next-generation devices that have the capacity to autonomously navigate aqueous environments.

Steady state-evoked potentials of subjective beat perception in musical rhythms

Synchronization of movement to music is a seemingly universal human capacity that depends on sustained beat perception. Previous research shows that the frequency of the beat can be observed in the neural activity of the listener. However, the extent to which these neural responses reflect concurrent, conscious perception of musical beat versus stimulus-driven activity is a matter of debate. We investigated whether this kind of periodic brain activity, measured using electroencephalography (EEG), reflects perception of beat, by holding the stimulus constant while manipulating the listener’s perception. Listeners with minimal music training heard a musical excerpt that strongly supported one of two beat patterns (context), followed by a rhythm consistent with either beat pattern (ambiguous phase). During the final phase, listeners indicated whether or not a superimposed drum matched the perceived beat (probe phase). Participants were more likely to indicate that the probe matched the music when that probe matched the original context, suggesting an ability to maintain the beat percept through the ambiguous phase. Likewise, we observed that the spectral amplitude during the ambiguous phase was higher at frequencies corresponding to the beat of the preceding context, and the EEG amplitude at the beat-related frequency predicted performance on the beat induction task on a single-trial basis. Together, these findings provide evidence that auditory cortical activity reflects conscious perception of musical beat and not just stimulus features or effortful attention.

Ccdc113/Ccdc96 complex, a novel regulator of ciliary beating that connects radial spoke 3 to dynein g and the nexin link

Ciliary beating requires the coordinated activity of numerous axonemal complexes. The protein composition and role of radial spokes (RS), nexin links (N-DRC) and dyneins (ODAs and IDAs) is well established. However, how information is transmitted from the central apparatus to the RS and across other ciliary structures remains unclear. Here, we identify a complex comprising the evolutionarily conserved proteins Ccdc96 and Ccdc113, positioned parallel to N-DRC and forming a connection between RS3, dynein g, and N-DRC. Although Ccdc96 and Ccdc113 can be transported to cilia independently, their stable docking and function requires the presence of both proteins. Deletion of either CCDC113 or CCDC96 alters cilia beating frequency, amplitude and waveform. We propose that the Ccdc113/Ccdc96 complex transmits signals from RS3 and N-DRC to dynein g and thus regulates its activity and the ciliary beat pattern.