Genetic background,and not ontogenetic effects,affects avian seasonal timing of reproduction

Avian seasonal timing is a life‐history trait with important fitness consequences and which is currently under directional selection due to climate change. To predict micro‐evolution in this trait, it is crucial to properly estimate its heritability. Heritabilities are often estimated from pedigreed wild populations. As these are observational data, it leaves the possibility that the resemblance between related individuals is not due to shared genes but to ontogenetic effects; when the environment for the offspring provided by early laying pairs differs from that by late pairs and the laying dates of these offspring when they reproduce themselves is affected by this environment, this may lead to inflated heritability estimates. Using simulation studies, we first tested whether and how much such an early environmental effect can inflate heritability estimates from animal models, and we showed that pedigree structure determines by how much early environmental effects inflate heritability estimates. We then used data from a wild population of great tits (Parus major) to compare laying dates of females born early in the season in first broods and from sisters born much later, in second broods. These birds are raised under very different environmental conditions but have the same genetic background. The laying dates of first and second brood offspring do not differ when they reproduce themselves, clearly showing that ontogenetic effects are very small and hence, family resemblance in timing is due to genes. This finding is essential for the interpretation of the heritabilities reported from wild populations and for predicting micro‐evolution in response to climate change.     

The influence of β-cyclodextrin on the kinetics of progesterone transformation by Rhizopus nigricans

The process of progesterone 11α-hydroxylation by the pelleted growth form of the filamentous fungus Rhizopus nigricans has been described with a mathematical model, based on Michaelis-Menten enzyme kinetics and the rate of substrate dissolution. It was confirmed that the low water solubility of steroids is the limiting step of this process at high steroid concentrations. In order to overcome this problem, β-cyclodextrin, which is known to form inclusion complexes with these organic compounds, was added to the production medium. The phase solubility of the steroid-β-cyclodextrin system was investigated and the effect of β-cyclodextrin addition on progesterone biotransformation evaluated. Enhancement of steroid solubility was demonstrated and nearly two-fold increase in reaction rate was found in the presence of β-cyclodextrin.     

On the Prediction of the Enantioselectivity of Candida rugosa Lipase by Comparative Molecular Field Analysis

Comparative molecular field analysis (CoMFA) was used to derive a quantitative substrate model for the enzymatic resolution of norbornanol esters by the lipase of Candida rugosa. Within these calculations, the steric and electrostatic interactions of both enantiomers and the differences in the corresponding two fields were used for the correlation of the substrate structure with the enantioselectivity of the hydrolysis. Different alignments of the molecules were used to improve the model.     

A Three-Dimensional Musculoskeletal Model of the Human Knee Joint. Part 2: Analysis of Ligament Function

A three-dimensional model of the knee is used to study ligament function during anterior-posterior (a-p) draw, axial rotation, and isometric contractions of the extensor and flexor muscles. The geometry of the model bones is based on cadaver data. The contacting surfaces of the femur and tibia are modeled as deformable; those of the femur and patella are assumed to be rigid. Twelve elastic elements are used to describe the geometry and mechanical properties of the cruciate ligaments, the collateral ligaments, and the posterior capsule. The model is actuated by thirteen musculotendinous units, each unit represented as a three-element muscle in series with tendon. The calculations show that the forces applied during a-p draw are substantially different from those applied by the muscles during activity. Principles of knee-ligament function based on the results of in vitro experiments may therefore be overstated. Knee-ligament forces during straight a-p draw are determined solely by the changing geometry of the ligaments relative to the bones: ACL force decreases with increasing flexion during anterior draw because the angle between the ACL and the tibial plateau decreases as knee flexion increases; PCL force increases with increasing flexion during posterior draw because the angle between the PCL and the tibial plateau increases. The pattern of ligament loading during activity is governed by the geometry of the muscles spanning the knee: the resultant force in the ACL during isometric knee extension is determined mainly by the changing orientation of the patellar tendon relative to the tibia in the sagittal plane; the resultant force in the PCL during isometric knee flexion is dominated by the angle at which the hamstrings meet the tibia in the sagittal plane.     

Bone Load Estimation for the Proximal Femur Using Single Energy Quantitative CT Data

A density-based load estimation method was applied to determine femoral load patterns. Two-dimensional finite element models were constructed using single energy quantitative computed tomography (QCT) data from two femora. basic load cases included parabolic pressure joint loads and constant tractions on the greater trochanter. An optimization procedure adjusted magnitudes of the basic load cases, such that the applied mechanical stimulus approached the ideal stimulus throughout each model. Dominant estimated load directions were generally consistent with published experimental data for gait. Other estimated loads suggested that loads at extreme joint orientations may be important to maintenance of bone structure. Remodeling simulations with the estimated loads produced density distributions qualitatively similar to the QCT data sets. Average nodal density errors between QCT data and predictions were 0·24 g/cm³ and 0·28 g/cm³. The results indicate that density-based load estimation could improve understanding of loading patterns on bones.     

Soft tissue structures resisting anterior instability in a computational glenohumeral joint model

The glenohumeral joint is the most dislocated joint in the body due to the lack of bony constraints and the dependence on soft tissue for stability. The roles that various structures provide to joint function are important for understanding injury treatment and orthopaedic device design purposes. The goal of this study was to develop a computational model of the glenohumeral joint whereby joint behaviour was dictated by articular contact, ligamentous constraints, muscle loading and external perturbations. The bone structure of the computational model consisted of assembled computer tomographic images of the scapula, humerus and clavicle. The soft tissue elements were composed of forces and tension-only springs that represented muscles and ligaments. Validation of this model was achieved by comparing computational predictions to the results of a cadaveric experiment in which the relative contribution of muscles and ligaments to anterior joint stability was examined. The computational model predicted an anterior subluxation force that was similar to the cadaveric experimental results in humeral external rotation. The individual structure results showed the subscapularis to be critical to stabilisation in both neutral and external rotations, the biceps stabilised the joint in neutral but not in external rotation, and the inferior glenohumeral ligament resisted anterior displacement only in external rotation. The model's predictions were similar to the conclusions of the cadaveric experiment and the literature. Knowledge gained from this type of model could assist in further understanding the contribution of soft tissue stabilisers to joint function, pre-operative planning or the design of orthopaedic implants.     

A muscle-path-plane method for representing muscle contraction during joint movement

Traditional muscle paths (the straight-line model and the viapoint-line model) emphasise either the mechanical properties that arouse joint movement or the morphological characteristics of the muscles. To consider both the factors, a muscle-path-plane (MPP) method is introduced to model the paths of muscles during joint movement. This method is based on the premise that there is a MPP, constructed by origin, insertion and MPP control point, which represents the major direction of the muscle contraction for an arbitrary joint configuration at any time. Then, we can calculate the functions and the lengths of the muscle paths during instantaneous joint movement in MPP by mathematical approaches. Taking the triceps brachii as an example, the lengths of its paths during elbow flexion are calculated and compared with the relative studies reported in the literature. It is concluded that this method can provide an insight into the simulation of the muscle contraction.     

An improved OpenSim gait model with multiple degrees of freedom knee joint and knee ligaments

Musculoskeletal models are widely used to investigate joint kinematics and predict muscle force during gait. However, the knee is usually simplified as a one degree of freedom joint and knee ligaments are neglected. The aim of this study was to develop an OpenSim gait model with enhanced knee structures. The knee joint in this study included three rotations and three translations. The three knee rotations and mediolateral translation were independent, with proximodistal and anteroposterior translations occurring as a function of knee flexion/extension. Ten elastic elements described the geometrical and mechanical properties of the anterior and posterior cruciate ligaments (ACL and PCL), and the medial and lateral collateral ligaments (MCL and LCL). The three independent knee rotations were evaluated using OpenSim to observe ligament function. The results showed that the anterior and posterior bundles of ACL and PCL (aACL, pACL and aPCL, pPCL) intersected during knee flexion. The aACL and pACL mainly provided force during knee flexion and adduction, respectively. The aPCL was slack throughout the range of three knee rotations; however, the pPCL was utilised for knee abduction and internal rotation. The LCL was employed for knee adduction and rotation, but was slack beyond 20° of knee flexion. The MCL bundles were mainly used during knee adduction and external rotation. All these results suggest that the functions of knee ligaments in this model approximated the behaviour of the physical knee and the enhanced knee structures can improve the ability to investigate knee joint biomechanics during various gait activities.     

A computational model of in vitro angiogenesis based on extracellular matrix fibre orientation

Recent interest in the process of vascularisation within the biomedical community has motivated numerous new research efforts focusing on the process of angiogenesis. Although the role of chemical factors during angiogenesis has been well documented, the role of mechanical factors, such as the interaction between angiogenic vessels and the extracellular matrix, remains poorly understood. In vitro methods for studying angiogenesis exist; however, measurements available using such techniques often suffer from limited spatial and temporal resolutions. For this reason, computational models have been extensively employed to investigate various aspects of angiogenesis. This paper outlines the formulation and validation of a simple and robust computational model developed to accurately simulate angiogenesis based on length, branching and orientation morphometrics collected from vascularised tissue constructs. Microvessels were represented as a series of connected line segments. The morphology of the vessels was determined by a linear combination of the collagen fibre orientation, the vessel density gradient and a random walk component. Excellent agreement was observed between computational and experimental morphometric data over time. Computational predictions of microvessel orientation within an anisotropic matrix correlated well with experimental data. The accuracy of this modelling approach makes it a valuable platform for investigating the role of mechanical interactions during angiogenesis.     

A Density Distribution Algorithm for Bone Incorporating Local Orthotropy,Modal Analysis and Theories of Cellular Solids

An algorithm for bone remodeling is presented which allows for both a redistribution of density and a continuous change of principal material directions for the orthotropic material properties of bone. It employs a modal analysis to add density for growth and a local effective strain based analysis to redistribute density. General re-distribution functions are presented. The model utilizes theories of cellular solids to relate density and strength. The code predicts the same general density distributions and local orthotropy as observed in reality.