The effects of lyophilization on flexural stiffness of extrasynovial and intrasynovial tendon

Tendon or ligament reconstructions often use autologous or allogenic tendons from either extrasynovial or intrasynovial sources. Allograft tendons must be lyophilized for preservation before transplantation, a process which can impact mechanical properties of the graft. Reconstituted graft properties that are similar to native tendon are desirable. Although tensile and compressive properties of tendons have been investigated, there is a paucity of information describing flexural properties of tendon, which can impact the gliding resistance. This study aims to design a testing method to quantify tendon flexural modulus, and investigate the effects of lyophilization/rehydration procedures on tendon flexibility. A total of 20 peroneus longus tendons (extrasynovial) and 20 flexor digitorum profundus tendons (intrasynovial) were collected. Ten of each tendon were processed with 5 freeze–thaw cycles followed by lyophilization and rehydration with saline solution (0.9%). Bend testing was conducted on tendons to quantify the flexural modulus with and without processing. As canine FDP tendons contain fibrous and fibrocartilaginous tissue regions, the flexural moduli were measured in both regions. Flexural modulus of rehydrated, lyophilized extrasynovial PL tendon was significantly lower than that of similarly processed intrasynovial FDP tendon (p < 0.001). Flexural moduli of both the fibrocartilaginous and non-fibrocartilaginous regions of intrasynovial tendon significantly increased after lyophilization (p < 0.001). The flexural modulus of the fibrocartilaginous region was significantly higher than that of the non-fibrocartilaginous region in intrasynovial tendon (p < 0.001). Lyophilization significantly increases the flexural modulus of extrasynovial and intrasynovial tendons, and flexural modulus differs significantly between these two tendon types. Increases in stiffness caused by lyophilization may impact the mechanical performance of the allograft in vivo.     

Importance of mechanics and kinematics in determining the stiffness contribution of the vertebral column during body-caudal-fin swimming in fishes

Whole-body stiffness in fishes has important consequences for swimming mode, speed and efficiency, but the contribution of vertebral column stiffness to whole-body stiffness is unclear. In our opinion, this lack of clarity is due in part to the lack of studies that have measured both in vitro mechanical properties of the vertebral column as well as in vivo vertebral kinematics in the same species. Some lack of clarity may also come from real variation in the mechanical role of the vertebral column across species. Previous studies, based on either mechanics or kinematics alone, suggest species-specific variation in vertebral column locomotor function that ranges from highly stiff regimes that contribute greatly to whole-body stiffness, and potentially act as a spring, to highly compliant regimes that only prohibit excessive flexion of the intervertebral joints. We review data collected in combined investigations of both mechanics and kinematics of three species, Myxine glutinosa, Acipenser transmontanus, and Morone saxatilis, to illustrate how mechanical testing within the context of the in vivo kinematics more clearly distinguishes the role of the vertebral column in each species. In addition, we identify species for which kinematic data are available, but mechanical data are lacking. We encourage further investigation of these species to fill these mechanical data gaps. Finally, we hope these future combined analyses will identify certain morphological, mechanical, or kinematic parameters that might be associated with certain vertebral column functional regimes with respect to body stiffness.     

The twist-to-bend compliance of the Rheum rhabarbarum petiole: integrated computations and experiments

Plant petioles can be considered as hierarchical cellular structures, displaying geometric features defined at multiple length scales. Their macroscopic mechanical properties are the cumulative outcome of structural properties attained at each level of the structural hierarchy. This work appraises the compliance of a rhubarb stalk by determining the stalk’s bending and torsional stiffness both computationally and experimentally. In our model, the irregular cross-sectional shape of the petiole and the layers of the constituent tissues are considered to evaluate the stiffness properties at the structural level. The arbitrary shape contour of the petiole is generated with reasonable accuracy by the Gielis superformula. The stiffness and architecture of the constituent layered tissues are modeled by using the concept of shape transformers so as to obtain the computational twist-to-bend ratio for the petiole. The rhubarb stalk exhibits a ratio of flexural to torsional stiffness 4.04 (computational) and 3.83 (experimental) in comparison with 1.5 for isotropic, incompressible, circular cylinders, values that demonstrate the relative structural compliance to flexure and torsion.     

Estimating fish swimming metrics and metabolic rates with accelerometers: the influence of sampling frequency

Accelerometry is growing in popularity for remotely measuring fish swimming metrics, but appropriate sampling frequencies for accurately measuring these metrics are not well studied. This research examined the influence of sampling frequency (1–25 Hz) with tri‐axial accelerometer biologgers on estimates of overall dynamic body acceleration (ODBA), tail‐beat frequency, swimming speed and metabolic rate of bonefish Albula vulpes in a swim‐tunnel respirometer and free‐swimming in a wetland mesocosm. In the swim tunnel, sampling frequencies of ≥ 5 Hz were sufficient to establish strong relationships between ODBA, swimming speed and metabolic rate. However, in free‐swimming bonefish, estimates of metabolic rate were more variable below 10 Hz. Sampling frequencies should be at least twice the maximum tail‐beat frequency to estimate this metric effectively, which is generally higher than those required to estimate ODBA, swimming speed and metabolic rate. While optimal sampling frequency probably varies among species due to tail‐beat frequency and swimming style, this study provides a reference point with a medium body‐sized sub‐carangiform teleost fish, enabling researchers to measure these metrics effectively and maximize study duration.     

Size-related effects and the influence of metabolic traits and morphology on swimming performance in fish

Energy metabolism fuels swimming and other biological processes. We compared the swimming performance and energy metabolism within and across eight freshwater fish species. Using swim tunnel respirometers, we measured the standard metabolic rate (SMR) and maximum metabolic rate (MMR) and calculated the critical swimming speed (U_crit). We accounted for body size, metabolic traits, and some morphometric ratios in an effort to understand the extent and underlying causes of variation. Body mass was largely the best predictor of swimming capacity and metabolic traits within species. Moreover, we found that predictive models using total length or SMR, in addition to body mass, significantly increased the explained variation of U_crit and MMR in certain fish species. These predictive models also underlined that, once body mass has been accounted for, U_crit can be independently affected by total length or MMR. This study exemplifies the utility of multiple regression models to assess within-species variability. At interspecific level, our results showed that variation in U_crit can partly be explained by the variation in the interrelated traits of MMR, fineness, and muscle ratios. Among the species studied, bleak Alburnus alburnus performed best in terms of swimming performance and efficiency. By contrast, pumpkinseed Lepomis gibbosus showed very poor swimming performance, but attained lower mass-specific cost of transport (MCOT) than some rheophilic species, possibly reflecting a cost reduction strategy to compensate for hydrodynamic disadvantages. In conclusion, this study provides insight into the key factors influencing the swimming performance of fish at both intra- and interspecific levels.     

Computational modeling of gene structure in Arabidopsis thaliana

Computational gene identification by sequence inspection remains a challenging problem. For a typical Arabidopsis thaliana gene with five exons, at least one of the exons is expected to have at least one of its borders predicted incorrectly by ab initio gene finding programs. More detailed analysis for individual genomic loci can often resolve the uncertainty on the basis of EST evidence or similarity to potential protein homologues. Such methods are part of the routine annotation process. However, because the EST and protein databases are constantly growing, in many cases original annotation must be re-evaluated, extended, and corrected on the basis of the latest evidence. The Arabidopsis Genome Initiative is undertaking this task on the whole-genome scale via its participating genome centers. The current Arabidopsis genome annotation provides an excellent starting point for assessing the protein repertoire of a flowering plant. More accurate whole-genome annotation will require the combination of high-throughput and individual gene experimental approaches and computational methods. The purpose of this article is to discuss tools available to an individual researcher to evaluate gene structure prediction for a particular locus.     

Foraging behaviour of planktivorous fish in artificial vegetation: the effects on swimming and feeding

In the littoral zones of lakes, aquatic macrophytes produce considerable structural variation that can provide protection to prey communities by hindering predator foraging activity. The swimming and feeding behaviour of a planktivore, Pseudorasbora parva(Cyprinidae) on its prey (Daphnia pulex) was studied in a series of laboratory experiments with varying densities (0, 350, 700, 1400, 2100 and 2800 stems m^–2) of simulated submerged vegetation. Prey availability was varied from 0.5, 1.0, 2.0, 5.0, 10.0 and 25.0 prey l^–1. As the stem density increased, the predator's swimming speed and the number of prey captured decreased relative to feeding in open water. A good relation existed between the number of successful prey captures and swimming speed with the average stem distance to fish body length ratio (D). An abrupt reduction in feeding and swimming was recorded when D was reduced to values less than one.     

Separate modeling of cortical and trabecular bone offers little improvement in FE predictions of local structural stiffness at the proximal tibia

Abstract

Quantitative computed tomography-based finite element (QCT-FE) modeling has potential to clarify the role of altered subchondral bone stiffness in osteoarthritis. The objective of this research was to evaluate different QCT-FE modeling and thresholding approaches to identify the method which best predicted experimentally measured local subchondral structural stiffness with highest explained variance and least error. Our results showed that separate modeling of proximal tibial cortical and trabecular bone offered little improvement in QCT-FE-predicted stiffness (0% to +3% improvement in explained variance) when compared to modeling the proximal tibia as a single structure. Based on the results of this study, we do not recommend separate modeling of cortical bone and trabecular bone when developing QCT-FE models of the proximal tibia for predicting subchondral bone stiffness.     

Cartesian stiffness for wrist joints: analysis on the Lie group of 3D rotations and geometric approximation for experimental evaluation

This paper is concerned with the analysis and the numerical evaluation from experimental measurements of the static, Cartesian stiffness of wrist joints, in particular the human wrist. The primary aim is to extend from Euclidean spaces to so(3), the group of rigid body rotations, previous methods for assessing the end-point stiffness of the human arm, typically performed via a robotic manipulandum. As a first step, the geometric definition of Cartesian stiffness from current literature is specialised to the group so(3). Emphasis is placed on the choice of the unique, natural, affine connection on so(3) which guarantees symmetry of the stiffness matrix in presence of conservative fields for any configuration, also out of equilibrium. As the main contribution of this study, a coordinate-independent approximation based on the geometric notion of geodesics is proposed which provides a working equation for evaluating stiffness directly from experimental measurements. Finally, a graphical representation of the stiffness is discussed which extends the ellipse method often used for end-point stiffness visualisation and which is suitable to compare stiffness matrices evaluated at different configurations.     

游泳对大鼠阳虚状态的影响及数理分析

目的考察一次性游泳对氢化可的松粉针剂诱导大鼠阳虚状态指标的影响,以期暴露模型本身内隐的隐性测评指标并确定特征指标。方法将SD雄性大鼠随机分为正常组、正常游泳组、阳虚组、阳虚游泳组,阳虚组／阳虚游泳组肌注氢化可的松粉针剂20ms／kg,正常组／正常游泳组注射等量的0．9％氯化钠溶液,注射14d后,阳虚游泳组／正常游泳组辅以一次性游泳后,各组麻醉,取血,测定相关指标。结果阳虚游泳组C4、cGMP、TC、L阳虚隐性指标暴露,BUN、17-OHCS、T、T／E2、cAMP／cGMP阳虚评定指标凸显。结论非破坏性一次游泳可以使氢化可的松粉针剂诱导的大鼠阳虚证候模型的隐性指标凸显、部分显性指标放大,建议今后在建立、模拟阳虚证候模型时辅以游泳手段,以便客观、全面、真实的反映模型状态。     

Mitochondria transfer reverses the inhibitory effects of low stiffness on osteogenic differentiation of human mesenchymal stem cells

Microenvironment biophysical factors such as matrix stiffness can noticeably affect the differentiation of mesenchymal stem cells (MSCs). In this mechanobiology transduction process, mitochondria are shown to be an active participant. The present study aims to systematically elucidate the phenotypic and functional changes of mitochondria during the stiffness-mediated osteogenic differentiation. Additionally, the effect of mitochondria transfer on the osteogenesis of impaired MSCs caused by stiffness was investigated. Human periodontal ligament stem cells (PDLSCs) were used as model cells in the current study. Low stiffness restrained the cell spreading and significantly inhibited the proliferation and osteogenic differentiation of PDLSCs. Mitochondria of PDLSCs cultured on low stiffness exhibited shorter length, rounded shape, fusion/fission imbalance, ROS and mitophagy level increase, and ATP production reduction. The inhibited mitochondria function and osteogenic differentiation capacity were recovered to near-normal levels after transferring the mitochondria of PDLSCs cultured on the high stiffness. This study indicated that low matrix stiffness altered the mitochondrial morphology and induced systematical mitochondrial dysfunction during the osteogenic differentiation of MSCs. Mitochondria transfer was proved to be a feasible technique for maintaining MSCs function in vitro by reversing the osteogenesis ability.     

Computational and mathematical models of chondrogenesis in vertebrate limbs

The production of cartilage (chondrogenic patterning) in the limb is one of the best‐studied examples of the emergence of form in developmental biology. At the core of the theoretical study is an effort to understand the mechanism that establishes the characteristic distribution of cartilage in the embryonic limb, which defines the future sites and shapes of bones that will be present in the mature limb. This review article gives an overview of the history and current state of a rich literature of mathematical and computational models that seek to contribute to this problem. We describe models for the mechanisms of limb growth and shaping via interaction with various chemical fields, as well as models addressing the intrinsic self‐organization capabilities of the embryonic mesenchymal tissue, such as reaction‐diffusion and mechanochemical models. We discuss the contributions of these models to the current understanding of chondrogenesis in vertebrate limbs, as well as their relation to the varied conceptual models that have been proposed by experimentalists. Birth Defects Research (Part C) 96:176–192, 2012. © 2012 Wiley Periodicals, Inc.     

Investigation of the age-at-onset heterogeneity in type 1 diabetes through mathematical modeling

The heterogeneity between young- and adult-onset type 1 diabetes (T1D) is well known, but not well understood. We approach this question through mathematical formulation and analysis of the dynamic interactions between the immune cells and the pancreatic islet beta-cells that lead to the beta-cell destruction. Utilizing the perturbation expansion method we investigate the dynamic stability of our system under fast and slow beta-cell turnover limits. We find that if autoimmunity is initiated when the turnover is slow (adult age), a stable steady state can exist with reduced number of beta-cells, where the beta-cell regeneration balances the ongoing autoimmune destruction. This implies that a slow disease process is possible. In contrast, if autoimmunity occurs when the beta-cell turnover is rapid (young age), such a stable state will never be attained and the destruction will progress unabated, leading to an acute disease onset. The major findings of our model are consistent with clinical observations, and it offers an explanation for the dynamic and phenotypic heterogeneity between young- and adult-onset T1D. More importantly, the model analyses point out that pathways regulating beta-cell turnover can be new targets to interfere with the disease process of T1D.     

Center of mass motion in swimming fish: effects of speed and locomotor mode during undulatory propulsion

Studies of center of mass (COM) motion are fundamental to understanding the dynamics of animal movement, and have been carried out extensively for terrestrial and aerial locomotion. But despite a large amount of literature describing different body movement patterns in fishes, analyses of how the center of mass moves during undulatory propulsion are not available. These data would be valuable for understanding the dynamics of different body movement patterns and the effect of differing body shapes on locomotor force production. In the present study, we analyzed the magnitude and frequency components of COM motion in three dimensions (x: surge, y: sway, z: heave) in three fish species (eel, bluegill sunfish, and clown knifefish) swimming with four locomotor modes at three speeds using high-speed video, and used an image cross-correlation technique to estimate COM motion, thus enabling untethered and unrestrained locomotion. Anguilliform swimming by eels shows reduced COM surge oscillation magnitude relative to carangiform swimming, but not compared to knifefish using a gymnotiform locomotor style. Labriform swimming (bluegill at 0.5 body lengths/s) displays reduced COM sway oscillation relative to swimming in a carangiform style at higher speeds. Oscillation frequency of the COM in the surge direction occurs at twice the tail beat frequency for carangiform and anguilliform swimming, but at the same frequency as the tail beat for gymnotiform locomotion in clown knifefish. Scaling analysis of COM heave oscillation for terrestrial locomotion suggests that COM heave motion scales with positive allometry, and that fish have relatively low COM oscillations for their body size.     

Regulation of step frequency in transtibial amputee endurance athletes using a running-specific prosthesis

Running specific prostheses (RSP) are designed to replicate the spring-like behaviour of the human leg during running, by incorporating a real physical spring in the prosthesis. Leg stiffness is an important parameter in running as it is strongly related to step frequency and running economy. To be able to select a prosthesis that contributes to the required leg stiffness of the athlete, it needs to be known to what extent the behaviour of the prosthetic leg during running is dominated by the stiffness of the prosthesis or whether it can be regulated by adaptations of the residual joints. The aim of this study was to investigate whether and how athletes with an RSP could regulate leg stiffness during distance running at different step frequencies.Seven endurance runners with an unilateral transtibial amputation performed five running trials on a treadmill at a fixed speed, while different step frequencies were imposed (preferred step frequency (PSF) and −15%, −7.5%, +7.5% and +15% of PSF). Among others, step time, ground contact time, flight time, leg stiffness and joint kinetics were measured for both legs.In the intact leg, increasing step frequency was accompanied by a decrease in both contact and flight time, while in the prosthetic leg contact time remained constant and only flight time decreased. In accordance, leg stiffness increased in the intact leg, but not in the prosthetic leg. Although a substantial contribution of the residual leg to total leg stiffness was observed, this contribution did not change considerably with changing step frequency.Amputee athletes do not seem to be able to alter prosthetic leg stiffness to regulate step frequency during running. This invariant behaviour indicates that RSP stiffness has a large effect on total leg stiffness and therefore can have an important influence on running performance. Nevertheless, since prosthetic leg stiffness was considerably lower than stiffness of the RSP, compliance of the residual leg should not be ignored when selecting RSP stiffness.     

Accuracy and reproducibility of bending stiffness measurements by mechanical response tissue analysis in artificial human ulnas

Osteoporosis is characterized by reduced bone strength, but no FDA-approved medical device measures bone strength. Bone strength is strongly associated with bone stiffness, but no FDA-approved medical device measures bone stiffness either. Mechanical Response Tissue Analysis (MRTA) is a non-significant risk, non-invasive, radiation-free, vibration analysis technique for making immediate, direct functional measurements of the bending stiffness of long bones in humans in vivo. MRTA has been used for research purposes for more than 20 years, but little has been published about its accuracy. To begin to investigate its accuracy, we compared MRTA measurements of bending stiffness in 39 artificial human ulna bones to measurements made by Quasistatic Mechanical Testing (QMT). In the process, we also quantified the reproducibility (i.e., precision and repeatability) of both methods. MRTA precision (1.0±1.0%) and repeatability (3.1±3.1%) were not as high as those of QMT (0.2±0.2% and 1.3+1.7%, respectively; both p<10⁻⁴). The relationship between MRTA and QMT measurements of ulna bending stiffness was indistinguishable from the identity line (p=0.44) and paired measurements by the two methods agreed within a 95% confidence interval of ±5%. If such accuracy can be achieved on real human ulnas in situ, and if the ulna is representative of the appendicular skeleton, MRTA may prove clinically useful.     

Different frequency control mechanisms and the exploitation of frequency space in passerines

1. Birdsong is used in reproductive context and, consequently, has been shaped by strong natural and sexual selection. The acoustic performance includes a multitude of acoustic and temporal characteristics that are thought to honestly reveal the quality of the singing individual.
2. One major song feature is frequency and its modulation. Sound frequency can be actively controlled, but the control mechanisms differ between different groups. Two described mechanisms are pressure‐driven frequency changes in suboscines and control by syringeal muscles in oscines.
3. To test to what degree these different control mechanisms enhance or limit the exploitation of frequency space by individual species and families, we compared the use of frequency space by tyrannid suboscines and emberizid/passerellid oscines.
4. We find that despite the different control mechanisms, the songs of species in both groups can contain broad frequency ranges and rapid and sustained frequency modulation (FM). The maximal values for these parameters are slightly higher in oscines.
5. Furthermore, the mean frequency range of song syllables is substantially larger in oscines than suboscines. Species within each family group collectively exploit equally broadly the available frequency space.
6. The narrower individual frequency ranges of suboscines likely indicate morphological specialization for particular frequencies, whereas muscular control of frequency facilitated broader exploitation of frequency space by individual oscine species.

     

Disentangling the functional roles of morphology and motion in the swimming of fish

In fishes the shape of the body and the swimming mode generally are correlated. Slender-bodied fishes such as eels, lampreys, and many sharks tend to swim in the anguilliform mode, in which much of the body undulates at high amplitude. Fishes with broad tails and a narrow caudal peduncle, in contrast, tend to swim in the carangiform mode, in which the tail undulates at high amplitude. Such fishes also tend to have different wake structures. Carangiform swimmers generally produce two staggered vortices per tail beat and a strong downstream jet, while anguilliform swimmers produce a more complex wake, containing at least two pairs of vortices per tail beat and relatively little downstream flow. Are these differences a result of the different swimming modes or of the different body shapes, or both? Disentangling the functional roles requires a multipronged approach, using experiments on live fishes as well as computational simulations and physical models. We present experimental results from swimming eels (anguilliform), bluegill sunfish (carangiform), and rainbow trout (subcarangiform) that demonstrate differences in the wakes and in swimming performance. The swimming of mackerel and lamprey was also simulated computationally with realistic body shapes and both swimming modes: the normal carangiform mackerel and anguilliform lamprey, then an anguilliform mackerel and carangiform lamprey. The gross structure of simulated wakes (single versus double vortex row) depended strongly on Strouhal number, while body shape influenced the complexity of the vortex row, and the swimming mode had the weakest effect. Performance was affected even by small differences in the wakes: both experimental and computational results indicate that anguilliform swimmers are more efficient at lower swimming speeds, while carangiform swimmers are more efficient at high speed. At high Reynolds number, the lamprey-shaped swimmer produced a more complex wake than the mackerel-shaped swimmer, similar to the experimental results. Finally, we show results from a simple physical model of a flapping fin, using fins of different flexural stiffness. When actuated in the same way, fins of different stiffnesses propel themselves at different speeds with different kinematics. Future experimental and computational work will need to consider the mechanisms underlying production of the anguilliform and carangiform swimming modes, because anguilliform swimmers tend to be less stiff, in general, than are carangiform swimmers.     

Strain imaging of the lateral collateral ligament using high frequency and conventional ultrasound imaging: An ex-vivo comparison

Recent first attempts of in situ ultrasound strain imaging in collateral ligaments encountered a number of challenges and illustrated a clear need for additional studies and more thorough validation of the available strain imaging methods. Therefore, in this study we experimentally validated ultrasound strain measurements of ex vivo human lateral collateral ligaments in an axial loading condition. Moreover, the use of high frequency ultrasound (>20 MHz) for strain measurement was explored and its performance compared to conventional ultrasound. The ligaments were stretched up to 5% strain and ultrasound measurements were compared to surface strain measurements from optical digital image correlation (DIC) techniques. The results show good correlations between ultrasound based and DIC based strain measures with R² values of 0.71 and 0.93 for high frequency and conventional ultrasound, subsequently. The performance of conventional ultrasound was significantly higher compared to high frequency ultrasound strain imaging, as the high frequency based method seemed more prone to errors. This study demonstrates that ultrasound strain imaging is feasible in ex vivo lateral collateral ligaments, which are relatively small structures. Additional studies should be designed for a more informed assessment of optimal in vivo strain measurements in collateral knee ligaments.     

Computational modeling of the catalytic reaction in triosephosphate isomerase

We present a comprehensive analysis of the catalytic cycle of the enzyme triosephosphate isomerase (TIM), including both the reactive chemistry and the catalytic loop and side-chain motions. Combining accurate mixed quantum mechanics/molecular mechanics (QM/MM) and protein structure prediction methods, we have modeled both the structural and chemical aspects of the reversible isomerization of dihydroxyacetone phosphate (DHAP) to d-glyceraldehyde 3-phosphate (GAP), for which there is a wealth of experimental data. The conjunction of this novel computational approach with the use of the recent near-atomic resolution TIM-DHAP Michaelis complex PDB structure, 1NEY.pdb, has enabled us to obtain robust qualitative and, where available, quantitative agreement with a wide range of experimental data. Among the principal conclusions that we are able to draw are the importance of the monoanionic (as opposed to dianioic) form of the substrate phosphate group in the catalytic cycle, detailed positioning and energetics of the key catalytic residues in the active-site, the flexible nature of Glu165, which favors its direct involvement in the formation of the enediol intermediate, energetics of the open and closed form of the catalytic loop region in the presence and absence of substrate, and quantitative reproduction of various experimentally measured reaction rates, typically to within approximately 1 kcal/mol. Our results are consistent with the available experimental data, and provide an initial picture as to why loop opening when GAP is the product has a higher barrier than when DHAP is the product.