A dental revolution: The association between occlusion and chewing behaviour

Dentistry is confronted with the functional and aesthetic consequences that result from an increased prevalence of misaligned and discrepant dental occlusal relations in modern industrialised societies. Previous studies have indicated that a reduction in jaw size in response to softer and more heavily processed foods during and following the Industrial Revolution (1,700 CE to present) was an important factor in increased levels of poor dental occlusion. The functional demands placed on the masticatory system play a crucial role in jaw ontogenetic development; however, the way in which chewing behaviours changed in response to the consumption of softer foods during this period remains poorly understood. Here we show that eating more heavily processed food has radically transformed occlusal power stroke kinematics. Results of virtual 3D analysis of the dental macrowear patterns of molars in 104 individuals dating to the Industrial Revolution (1,700–1,900 CE), and 130 of their medieval and early post-medieval antecedents (1,100–1,700 CE) revealed changes in masticatory behaviour that occurred during the early stages of the transition towards eating more heavily processed foods. The industrial-era groups examined chewed with a reduced transverse component of jaw movement. These results show a diminished sequence of occlusal contacts indicating that a dental revolution has taken place in modern times, involving a dramatic shift in the way in which teeth occlude and wear during mastication. Molar macrowear suggests a close connection between progressive changes in chewing since the industrialization of food production and an increase in the prevalence of poor dental occlusion in modern societies.

Twist and chew: three-dimensional tongue kinematics during chewing in macaque primates

Three-dimensional (3D) tongue movements are central to performance of feeding functions by mammals and other tetrapods, but 3D tongue kinematics during feeding are poorly understood. Tongue kinematics were recorded during grape chewing by macaque primates using biplanar videoradiography. Complex shape changes in the tongue during chewing are dominated by a combination of flexion in the tongue's sagittal planes and roll about its long axis. As hypothesized for humans, in macaques during tongue retraction, the middle (molar region) of the tongue rolls to the chewing (working) side simultaneous with sagittal flexion, while the tongue tip flexes to the other (balancing) side. Twisting and flexion reach their maxima early in the fast close phase of chewing cycles, positioning the food bolus between the approaching teeth prior to the power stroke. Although 3D tongue kinematics undoubtedly vary with food type, the mechanical role of this movement—placing the food bolus on the post-canine teeth for breakdown—is likely to be a powerful constraint on tongue kinematics during this phase of the chewing cycle. The muscular drivers of these movements are likely to include a combination of intrinsic and extrinsic tongue muscles.

A hold-and-feed mechanism drives directional DNA loop extrusion by condensin

SMC protein complexes structure genomes by extruding DNA loops, but the molecular mechanism that underlies their activity has remained unknown. We show that the active condensin complex entraps the bases of a DNA loop in two separate chambers. Single-molecule and cryo-electron microscopy provide evidence for a power-stroke movement at the first chamber that feeds DNA into the SMC-kleisin ring upon ATP binding, while the second chamber holds on upstream of the same DNA double helix. Unlocking the strict separation of 'motor' and 'anchor' chambers turns condensin from a one-sided into a bidirectional DNA loop extruder. We conclude that the orientation of two topologically bound DNA segments during the course of the SMC reaction cycle determines the directionality of DNA loop extrusion.

Observation and analysis of diving beetle movements while swimming

The fast swimming speed, flexible cornering, and high propulsion efficiency of diving beetles are primarily achieved by their two powerful hind legs. Unlike other aquatic organisms, such as turtle, jellyfish, fish and frog et al., the diving beetle could complete retreating motion without turning around, and the turning radius is small for this kind of propulsion mode. However, most bionic vehicles have not contained these advantages, the study about this propulsion method is useful for the design of bionic robots. In this paper, the swimming videos of the diving beetle, including forwarding, turning and retreating, were captured by two synchronized high-speed cameras, and were analyzed via SIMI Motion. The analysis results revealed that the swimming speed initially increased quickly to a maximum at 60% of the power stroke, and then decreased. During the power stroke, the diving beetle stretched its tibias and tarsi, the bristles on both sides of which were shaped like paddles, to maximize the cross-sectional areas against the water to achieve the maximum thrust. During the recovery stroke, the diving beetle rotated its tarsi and folded the bristles to minimize the cross-sectional areas to reduce the drag force. For one turning motion (turn right about 90 degrees), it takes only one motion cycle for the diving beetle to complete it. During the retreating motion, the average acceleration was close to 9.8 m/s2 in the first 25 ms. Finally, based on the diving beetle's hind-leg movement pattern, a kinematic model was constructed, and according to this model and the motion data of the joint angles, the motion trajectories of the hind legs were obtained by using MATLAB. Since the advantages of this propulsion method, it may become a new bionic propulsion method, and the motion data and kinematic model of the hind legs will be helpful in the design of bionic underwater unmanned vehicles.

Quantification and demonstration of the collective constriction-by-ratchet mechanism in the dynamin molecular motor

Dynamin oligomerizes into helical filaments on tubular membrane templates and, through constriction, cleaves them in a GTPase-driven way. Structural observations of GTP-dependent cross-bridges between neighboring filament turns have led to the suggestion that dynamin operates as a molecular ratchet motor. However, the proof of such mechanism remains absent. Particularly, it is not known whether a powerful enough stroke is produced and how the motor modules would cooperate in the constriction process. Here, we characterized the dynamin motor modules by single-molecule Förster resonance energy transfer (smFRET) and found strong nucleotide-dependent conformational preferences. Integrating smFRET with molecular dynamics simulations allowed us to estimate the forces generated in a power stroke. Subsequently, the quantitative force data and the measured kinetics of the GTPase cycle were incorporated into a model including both a dynamin filament, with explicit motor cross-bridges, and a realistic deformable membrane template. In our simulations, collective constriction of the membrane by dynamin motor modules, based on the ratchet mechanism, is directly reproduced and analyzed. Functional parallels between the dynamin system and actomyosin in the muscle are seen. Through concerted action of the motors, tight membrane constriction to the hemifission radius can be reached. Our experimental and computational study provides an example of how collective motor action in megadalton molecular assemblies can be approached and explicitly resolved.

A DNA packaging motor inchworms along one strand allowing it to adapt to alternative double-helical structures

Ring ATPases that translocate disordered polymers possess lock-washer architectures that they impose on their substrates during transport via a hand-over-hand mechanism. Here, we investigate the operation of ring motors that transport ordered, helical substrates, such as the bacteriophage ϕ29 dsDNA packaging motor. This pentameric motor alternates between an ATP loading dwell and a hydrolysis burst wherein it packages one turn of DNA in four steps. When challenged with DNA-RNA hybrids and dsRNA, the motor matches its burst to the shorter helical pitches, keeping three power strokes invariant while shortening the fourth. Intermittently, the motor loses grip on the RNA-containing substrates, indicating that it makes optimal load-bearing contacts with dsDNA. To rationalize these observations, we propose a helical inchworm translocation mechanism in which, during each cycle, the motor increasingly adopts a lock-washer structure during the ATP loading dwell and successively regains its planar form with each power stroke during the burst.

A reverse stroke characterizes the force generation of cardiac myofilaments, leading to an understanding of heart function

Changes in the molecular properties of cardiac myosin strongly affect the interactions of myosin with actin that result in cardiac contraction and relaxation. However, it remains unclear how myosin molecules work together in cardiac myofilaments and which properties of the individual myosin molecules impact force production to drive cardiac contractility. Here, we measured the force production of cardiac myofilaments using optical tweezers. The measurements revealed that stepwise force generation was associated with a higher frequency of backward steps at lower loads and higher stall forces than those of fast skeletal myofilaments. To understand these unique collective behaviors of cardiac myosin, the dynamic responses of single cardiac and fast skeletal myosin molecules, interacting with actin filaments, were evaluated under load. The cardiac myosin molecules switched among three distinct conformational positions, ranging from pre– to post–power stroke positions, in 1 mM ADP and 0 to 10 mM phosphate solution. In contrast to cardiac myosin, fast skeletal myosin stayed primarily in the post–power stroke position, suggesting that cardiac myosin executes the reverse stroke more frequently than fast skeletal myosin. To elucidate how the reverse stroke affects the force production of myofilaments and possibly heart function, a simulation model was developed that combines the results from the single-molecule and myofilament experiments. The results of this model suggest that the reversal of the cardiac myosin power stroke may be key to characterizing the force output of cardiac myosin ensembles and possibly to facilitating heart contractions.

Evolution of mechanical cooperativity among myosin II motors

Myosin II is a biomolecular machine that is responsible for muscle contraction. Myosin II motors act cooperatively: during muscle contraction, multiple motors bind to a single actin filament and pull it against an external load, like people pulling on a rope in a tug-of-war. We model the dynamics of actomyosin filaments in order to study the evolution of motor–motor cooperativity. We find that filament backsliding—the distance an actin slides backward when a motor at the end of its cycle releases—is central to the speed and efficiency of muscle contraction. Our model predicts that this backsliding has been reduced through evolutionary adaptations to the motor’s binding propensity, the strength of the motor’s power stroke, and the force dependence of the motor’s release from actin. These properties optimize the collective action of myosin II motors, which is not a simple sum of individual motor actions. The model also shows that these evolutionary variables can explain the speed–efficiency trade-off observed across different muscle tissues. This is an example of how evolution can tune the microscopic properties of individual proteins in order to optimize complex biological functions.

Ciliary Ca2+ pumps regulate intraciliary Ca2+ from the action potential and may co-localize with ciliary voltage-gated Ca2+ channels

ABSTRACT Calcium ions (Ca2+) entering cilia through the ciliary voltage-gated calcium channels (CaV) during the action potential causes reversal of the ciliary power stroke and backward swimming in Paramecium tetraurelia. How calcium is returned to the resting level is not yet clear. Our focus is on calcium pumps as a possible mechanism. There are 23 P. tetraurelia genes for calcium pumps that are members of the family of plasma membrane Ca2+ ATPases (PMCAs). They have domains homologous to those found in mammalian PMCAs. Of the 13 pump proteins previously identified in cilia, ptPMCA2a and ptPMCA2b are most abundant in the cilia. We used RNAi to examine which PMCA might be involved in regulating intraciliary Ca2+ after the action potential. RNAi for only ptPMCA2a and ptPMCA2b causes cells to significantly prolong their backward swimming, which indicates that Ca2+ extrusion in the cilia is impaired when these PMCAs are depleted. We used immunoprecipitations (IP) to find that ptPMCA2a and ptPMCA2b are co-immunoprecipitated with the CaV channel α1 subunits that are found only in the cilia. We used iodixanol (OptiPrep) density gradients to show that ptPMCA2a and ptPMCA2b and CaV1c are found in the same density fractions. These results suggest that ptPMCA2a and ptPMCA2b are located in the proximity of ciliary CaV channels.

Quantitative real-time analysis of the efflux by the MacAB-TolC tripartite efflux pump clarifies the role of ATP hydrolysis within mechanotransmission mechanism

Tripartite efflux pumps built around ATP-binding cassette (ABC) transporters are membrane protein machineries that perform vectorial export of a large variety of drugs and virulence factors from Gram negative bacteria, using ATP-hydrolysis as energy source. Determining the number of ATP molecules consumed per transport cycle is essential to understanding the efficiency of substrate transport. Using a reconstituted pump in a membrane mimic environment, we show that MacAB-TolC from Escherichia coli couples substrate transport to ATP-hydrolysis with high efficiency. Contrary to the predictions of the currently prevailing “molecular bellows” model of MacB-operation, which assigns the power stroke to the ATP-binding by the nucleotide binding domains of the transporter, by utilizing a novel assay, we report clear synchronization of the substrate transfer with ATP-hydrolysis, suggesting that at least some of the power stroke for the substrate efflux is provided by ATP-hydrolysis. Our findings narrow down the window for energy consumption step that results in substrate transition into the TolC-channel, expanding the current understanding of the efflux cycle of the MacB-based tripartite assemblies. Based on that we propose a modified model of the MacB cycle within the context of tripartite complex assembly.