Form-function relationships underlie rapid dietary changes in a lizard.

Macroevolutionary changes such as variation in habitat use or diet are often associated with convergent, adaptive changes in morphology. However, it is still unclear how small-scale morphological variation at the population level can drive shifts in ecology such as observed at a macroevolutionary scale. Here, we address this question by investigating how variation in cranial form and feeding mechanics relate to rapid changes in diet in an insular lizard (Podarcis siculus) after experimental introduction into a new environment. We first quantified differences in the skull shape and jaw muscle architecture between the source and introduced population using three-dimensional geometric morphometrics and dissections. Next, we tested the impact of the observed variation in morphology on the mechanical performance of the masticatory system using computer-based biomechanical simulation techniques. Our results show that small differences in shape, combined with variation in muscle architecture, can result in significant differences in performance allowing access to novel trophic resources. The confrontation of these data with the already described macroevolutionary relationships between cranial form and function in these insular lizards provides insights into how selection can, over relatively short time scales, drive major changes in ecology through its impact on mechanical performance.

A lesson unlearned? Underestimating tree cover in drylands biases global restoration maps.

Two recent global maps of tree restoration potential have identified vast regions where tree cover could be increased, ranging from 0.9 to 2.3 billion hectares. Both maps, however, emphasized dryland regions, with arid biomes making up 36%-42% of potential restoration area. Dryland biomes have repeatedly been recognized as inappropriate regions for expanding tree cover due to the risks of biodiversity loss, water overconsumption, and fire, so maps that highlight these regions for restoration must sustain careful scrutiny. Here, I show that both recent attempts to map restoration potential in arid regions have been hindered by underlying errors in the global tree cover maps they used. Systematic underestimates of existing sparse tree cover led directly to large overestimates of the potential for tree recovery in drylands. The Atlas of Forest Landscape Restoration Opportunities (Laestadius et al., Unasylva, 2011, 62, 47) overestimated tree restoration potential across a third of arid biomes by between 7% and 20% (55-166 million hectares [Mha]). Similarly, Bastin, Finegold, Garcia, Mollicone, et al. (Science, 2019, 365, 76) overestimated tree restoration potential across all arid biomes by 33%-45% (316-440 Mha). These inaccuracies limit the utility of this research for policy decisions in drylands and overstate the potential for tree planting to address climate change. Given this long-standing but underappreciated challenge in mapping global tree cover, I propose various ways forward that keep this lesson in mind. To better monitor and restore tree cover, I call for re-interpretation and correction of existing global maps, and for a new focus on quantifying sparse tree cover in drylands and other systems.

A biomechanical analysis of prognathous and orthognathous insect head capsules: evidence for a many-to-one mapping of form to function.

Insect head shapes are remarkably variable, but the influences of these changes on biomechanical performance are unclear. Among 'basal' winged insects, such as dragonflies, mayflies, earwigs and stoneflies, some of the most prominent anatomical changes are the general mouthpart orientation, eye size and the connection of the endoskeleton to the head. Here, we assess these variations as well as differing ridge and sclerite configurations using modern engineering methods including multibody dynamics modelling and finite element analysis in order to quantify and compare the influence of anatomical changes on strain in particular head regions and the whole head. We show that a range of peculiar structures such as the genal/subgenal, epistomal and circumocular areas are consistently highly loaded in all species, despite drastically differing morphologies in species with forward-projecting (prognathous) and downward-projecting (orthognathous) mouthparts. Sensitivity analyses show that the presence of eyes has a negligible influence on head capsule strain if a circumocular ridge is present. In contrast, the connection of the dorsal endoskeletal arms to the head capsule especially affects overall head loading in species with downward-projecting mouthparts. Analysis of the relative strains between species for each head region reveals that concerted changes in head substructures such as the subgenal area, the endoskeleton and the epistomal area lead to a consistent relative loading for the whole head capsule and vulnerable structures such as the eyes. It appears that biting-chewing loads are managed by a system of strengthening ridges on the head capsule irrespective of the general mouthpart and head orientation. Concerted changes in ridge and endoskeleton configuration might allow for more radical anatomical changes such as the general mouthpart orientation, which could be an explanation for the variability of this trait among insects. In an evolutionary context, many-to-one mapping of strain patterns onto a relatively similar overall head loading indeed could have fostered the dynamic diversification processes seen in insects.

Genetic markers of treatment response to tumour necrosis factor-α inhibitors in the treatment of psoriasis.

BACKGROUND: Anti-tumour necrosis factor (TNF)-α therapies have revolutionized the treatment of psoriasis; however, up to 50% of patients do not respond satisfactorily. Identification of pharmacogenetic markers of treatment response is an important stop in the development of individually tailored treatment. The objective of this study was to assess the association of human leucocyte antigen (HLA)-C, killer immunoglobulin receptor (KIR) and vitamin D receptor (VDR) genotypes with response to treatment by etanercept and adalimumab. METHODS: This was a study of 138 patients with severe chronic plaque psoriasis who were treated with etanercept and/or adalimumab. Patients were classified as responders if they achieved a 75% reduction in PASI (PASI75) or were almost clear of psoriasis after 24 weeks of therapy. The frequencies of HLA-C and KIR haplotypes and VDR polymorphisms were compared in responders and nonresponders. The frequency of all HLA-C and KIR genotypes were compared between the 138 patients with psoriasis and 247 healthy donors. RESULTS: The number of patients classified as responders was 46 of 94 (49%) in the etanercept group and 50 of 76 (66%) in the adalimumab group. None of the HLA-C, KIR or VDR genotypes examined was predictive of treatment response. Compared with healthy controls, patients with psoriasis were more likely to have the HLA-C*06 genotype (P < 0.001) and less likely to have the HLA-C*07 genotype (P < 0.001), whereas there was no significant difference in frequencies of any KIR subtype. CONCLUSIONS: Using the candidate gene approach to identify biomarkers of treatment response in psoriasis may have limited utility. This was a small study with limited power. Future larger studies are needed to further examine these findings and to explore alternative approaches to identify predictors of treatment response to biological agents.

Ultrasound assessment of the infrapatellar fat pad can detect Hoffa-synovitis in patients following anterior cruciate ligament reconstruction: A pilot study.

Introduction: Osteoarthritis (OA) commonly occurs following anterior cruciate ligament reconstruction (ACLR), affecting over 50 % of patients within 10-15 years post-ACLR. The Hoffa-synovitis of the infrapatellar fat pad (IPFP) has been implicated as a major contributor to OA pathogenesis. While MRI is typically used to evaluate the IPFP, it is cost-prohibitive for routine screening. This study aimed to validate ultrasound as an alternative for detecting IPFP Hoffa-synovitis in participants post-ACLR. Methods: In this cross-sectional study, 15 participants (18-35 years, 1-5 years post-ACLR) underwent two imaging sessions separated by one week. First, a standardized bilateral anterior knee ultrasound assessment was used to examine IPFP echo-intensity. Second, MRI scans of both knees were graded by a board-certified musculoskeletal radiologist for Hoffa-synovitis according to the Anterior Cruciate Ligament Osteoarthritis Score grading system. IPFP echo-intensity were quantified on each ultrasound image, and a limb symmetry index (LSI) was calculated to assess between-limb differences. We used an independent t-test and Cohen's d effect sizes to compare IPFP echo-intensity LSI between people with and without MRI-confirmed Hoffa-synovitis. Results: Four of the 15 participants (27 %) exhibited MRI-confirmed Hoffa-synovitis. Significantly higher IPFP echo-intensity LSI values were found in participants with Hoffa-synovitis (32.1 ± 12.1 %) compared to those without (10.5 ± 10.4 %), confirming the ultrasound's ability to distinguish between the two groups (t = -3.44; p = 0.004; d = 2.01). Discussion: Ultrasound detects bilateral IPFP signal intensity alterations in participants post-ACLR with MRI-confirmed Hoffa-synovitis. This work should be seen as a proof-of-concept, and further validation in a larger, more diverse sample is essential for verifying these results.

Masticatory loadings and cranial deformation in Macaca fascicularis: a finite element analysis sensitivity study.

Biomechanical analyses are commonly conducted to investigate how craniofacial form relates to function, particularly in relation to dietary adaptations. However, in the absence of corresponding muscle activation patterns, incomplete muscle data recorded experimentally for different individuals during different feeding tasks are frequently substituted. This study uses finite element analysis (FEA) to examine the sensitivity of the mechanical response of a Macaca fascicularis cranium to varying muscle activation patterns predicted via multibody dynamic analysis. Relative to the effects of varying bite location, the consequences of simulated variations in muscle activation patterns and of the inclusion/exclusion of whole muscle groups were investigated. The resulting cranial deformations were compared using two approaches; strain maps and geometric morphometric analyses. The results indicate that, with bite force magnitude controlled, the variations among the mechanical responses of the cranium to bite location far outweigh those observed as a consequence of varying muscle activations. However, zygomatic deformation was an exception, with the activation levels of superficial masseter being most influential in this regard. The anterior portion of temporalis deforms the cranial vault, but the remaining muscles have less profound effects. This study for the first time systematically quantifies the sensitivity of an FEA model of a primate skull to widely varying masticatory muscle activations and finds that, with the exception of the zygomatic arch, reasonable variants of muscle loading for a second molar bite have considerably less effect on cranial deformation and the resulting strain map than does varying molar bite point. The implication is that FEA models of biting crania will generally produce acceptable estimates of deformation under load as long as muscle activations and forces are reasonably approximated. In any one FEA study, the biological significance of the error in applied muscle forces is best judged against the magnitude of the effect that is being investigated.

Intraluminal thrombus has a selective influence on matrix metalloproteinases and their inhibitors (tissue inhibitors of matrix metalloproteinases) in the wall of abdominal aortic aneurysms.

BACKGROUND: The influence of intraluminal thrombus (ILT) on the proteolytic environment within the wall of an abdominal aortic aneurysm (AAA) is unknown. This is the first study to examine the correlation between ILT thickness and the levels of matrix metalloproteinases (MMPs) and their natural inhibitors (tissue inhibitors of matrix metalloproteinases [TIMPs]) within the adjacent AAA wall. METHODS: Thirty-five patients undergoing elective repair of AAAs were studied. A single full-thickness infrarenal aortic sample was obtained uniformly from the arteriotomy site from each patient. All samples were snap frozen and analyzed for total and active MMP 2, 8, and 9 and TIMP 1 and 2. Thrombus thickness at the specimen site was measured on the preoperative contrast computed tomographic angiograms. RESULTS: There was a statistically significant correlation between ILT thickness, concentration of TIMP 1, and active concentration of MMP 9. MMP 2 (active and total) and TIMP 2 demonstrated a positive correlation with ILT thickness, although not statistically significant. CONCLUSION: In this novel study, we found a significant positive correlation of ILT thickness with active MMP 9 and TIMP 1 concentration in the adjacent AAA wall, and this may have implications for AAA expansion and eventual rupture.

Modeling and control of anterior-posterior and medial-lateral sways in standing posture.

To study essential anterior-posterior and medial-lateral sways of the stance caused by rotational movements about the ankle and hip joints, a mathematical model is developed for the 3D postural kinematics and dynamics. The model is in the form of nonlinear differential-algebraic equations corresponding to a biomechanical system with holonomic constraints. A nonlinear feedback control law is further derived for stabilizing the upright stance, whilst eliminating internal torques induced by the constraints on postural movements. Numerical simulations of the model parametrized with experimental data of human body segments illustrate the performance of postural balancing with the proposed control.

Finite element modelling of squirrel, guinea pig and rat skulls: using geometric morphometrics to assess sensitivity.

Rodents are defined by a uniquely specialized dentition and a highly complex arrangement of jaw-closing muscles. Finite element analysis (FEA) is an ideal technique to investigate the biomechanical implications of these specializations, but it is essential to understand fully the degree of influence of the different input parameters of the FE model to have confidence in the model's predictions. This study evaluates the sensitivity of FE models of rodent crania to elastic properties of the materials, loading direction, and the location and orientation of the models' constraints. Three FE models were constructed of squirrel, guinea pig and rat skulls. Each was loaded to simulate biting on the incisors, and the first and the third molars, with the angle of the incisal bite varied over a range of 45°. The Young's moduli of the bone and teeth components were varied between limits defined by findings from our own and previously published tests of material properties. Geometric morphometrics (GMM) was used to analyse the resulting skull deformations. Bone stiffness was found to have the strongest influence on the results in all three rodents, followed by bite position, and then bite angle and muscle orientation. Tooth material properties were shown to have little effect on the deformation of the skull. The effect of bite position varied between species, with the mesiodistal position of the biting tooth being most important in squirrels and guinea pigs, whereas bilateral vs. unilateral biting had the greatest influence in rats. A GMM analysis of isolated incisor deformations showed that, for all rodents, bite angle is the most important parameter, followed by elastic properties of the tooth. The results here elucidate which input parameters are most important when defining the FE models, but also provide interesting glimpses of the biomechanical differences between the three skulls, which will be fully explored in future publications.

Validation of a morphometric reconstruction technique applied to a juvenile pelvis.

Three-dimensional reconstructions of bone geometry from microCT (computed tomography) data are frequently used in biomechanical and finite element analyses. Digitization of bone models is usually a simple process for specimens with a complete geometry, but in instances of damage or disarticulation it can be very challenging. Subsequent to digitization, further imaging techniques are often required to estimate the geometry of missing bone or connecting cartilage. This paper presents an innovative approach to the reconstruction of incomplete scan data, to reproduce proper anatomical arrangements of bones, including absent connecting cartilaginous elements. Utilizing geometric morphometric tools, the reconstruction technique is validated through comparison of a reconstructed 9 year old pelvis, to the original CT data. A principal component analysis and an overlay of the two pelves provide a measure of the accuracy of the reconstructed model. Future work aims to investigate the biomechanical effects of any minor positional error on the bone's predicted structural properties through the use of finite element analysis.

Assessments of bilateral asymmetry with application in human skull analysis.

As a common feature, bilateral symmetry of biological forms is ubiquitous, but in fact rarely exact. In a setting of analytic geometry, bilateral symmetry is defined with respect to a point, line or plane, and the well-known notions of fluctuating asymmetry, directional asymmetry and antisymmetry are recast. A meticulous scheme for asymmetry assessments is proposed and explicit solutions to them are derived. An investigation into observational errors of points representing the geometric structure of an object offers a baseline reference for asymmetry assessment of the object. The proposed assessments are applicable to individual, part or all point pairs at both individual and collective levels. The exact relationship between the developed treatments and the widely used Procrustes method in asymmetry assessment is examined. An application of the proposed assessments to a large collection of human skull data in the form of 3D landmark coordinates finds: (a) asymmetry of most skulls is not fluctuating, but directional if measured about a plane fitted to shared landmarks or side landmarks for balancing; (b) asymmetry becomes completely fluctuating if one side of a skull could be slightly rotated and translated with respect to the other side; (c) female skulls are more asymmetric than male skulls. The methodology developed in this study is rigorous and transparent, and lays an analytical base for investigation of structural symmetries and asymmetries in a wide range of biological and medical applications.

Masticatory loading and bone adaptation in the supraorbital torus of developing macaques.

Research on the evolution and adaptive significance of primate craniofacial morphologies has focused on adult, fully developed individuals. Here, we investigate the possible relationship between the local stress environment arising from masticatory loadings and the emergence of the supraorbital torus in the developing face of the crab-eating macaque Macaca fascicularis. By using finite element analysis (FEA), we are able to evaluate the hypothesis that strain energy density (SED) magnitudes are high in subadult individuals with resulting bone growth in the supraorbital torus. We developed three micro-CT-based FEA models of M. fascicularis skulls ranging in dental age from deciduous to permanent dentitions and validated them against published experimental data. Applied masticatory muscle forces were estimated from physiological cross-sectional areas of macaque cadaveric specimens. The models were sequentially constrained at each working side tooth to simulate the variation of the bite point applied during masticatory function. Custom FEA software was used to solve the voxel-based models and SED and principal strains were computed. A physiological superposition SED map throughout the face was created by allocating to each element the maximum SED value from each of the load cases. SED values were found to be low in the supraorbital torus region throughout ontogeny, while they were consistently high in the zygomatic arch and infraorbital region. Thus, if the supraorbital torus arises to resist masticatory loads, it is either already adapted in each of our subadult models so that we do not observe high SED or a lower site-specific bone deposition threshold must apply.

Combined finite element and multibody dynamics analysis of biting in a Uromastyx hardwickii lizard skull.

Lizard skulls vary greatly in shape and construction, and radical changes in skull form during evolution have made this an intriguing subject of research. The mechanics of feeding have surely been affected by this change in skull form, but whether this is the driving force behind the change is the underlying question that we are aiming to address in a programme of research. Here we have implemented a combined finite element analysis (FEA) and multibody dynamics analysis (MDA) to assess skull biomechanics during biting. A skull of Uromastyx hardwickii was assessed in the present study, where loading data (such as muscle force, bite force and joint reaction) for a biting cycle were obtained from an MDA and applied to load a finite element model. Fifty load steps corresponding to bilateral biting towards the front, middle and back of the dentition were implemented. Our results show the importance of performing MDA as a preliminary step to FEA, and provide an insight into the variation of stress during biting. Our findings show that higher stress occurs in regions where cranial sutures are located in functioning skulls, and as such support the hypothesis that sutures may play a pivotal role in relieving stress and producing a more uniform pattern of stress distribution across the skull. Additionally, we demonstrate how varying bite point affects stress distributions and relate stress distributions to the evolution of metakinesis in the amniote skull.

Rigid-body analysis of a lizard skull: modelling the skull of Uromastyx hardwickii.

Lizard skulls vary greatly in their detailed morphology. Theoretical models and practical studies have posited a definite relationship between skull morphology and bite performance, but this can be difficult to demonstrate in vivo. Computer modelling provides an alternative approach, as long as hard and soft tissue components can be integrated and the model can be validated. An anatomically accurate three-dimensional computer model of an Uromastyx hardwickii skull was developed for rigid-body dynamic analysis. The Uromastyx jaw was first opened under motion control, and then muscle forces were applied to produce biting simulations where bite forces and joint forces were calculated. Bite forces comparable to those reported in the literature were predicted, and detailed muscular force information was produced along with additional information on the stabilizing role of temporal ligaments in late jaw closing.

Development of a (silent) speech recognition system for patients following laryngectomy.

Surgical voice restoration post-laryngectomy has a number of limitations and drawbacks. The present gold standard involves the use of a tracheo-oesophageal fistula (TOF) valve to divert air from the lungs into the throat, which vibrates, and from this, speech can be formed. Not all patients can use these valves and those who do are susceptible to complications associated with valve failure. Thus there is still a place for other voice restoration options. With advances in electronic miniaturization and portable computing power a computing-intensive solution has been investigated. Magnets were placed on the lips, teeth and tongue of a volunteer causing a change in the surrounding magnetic field when the individual mouthed words. These changes were detected by 6 dual axis magnetic sensors, which were incorporated into a pair of special glasses. The resulting signals were compared to training data recorded previously by means of a dynamic time warping algorithm using dynamic programming. When compared to a small vocabulary database, the patterns were found to be recognised with an accuracy of 97% for words and 94% for phonemes. On this basis we plan to develop a speech system for patients who have lost laryngeal function.

New insights into the biomechanics of Legg-Calvé-Perthes' disease: The Role of Epiphyseal Skeletal Immaturity in Vascular Obstruction.

OBJECTIVES: Legg-Calvé-Perthes' disease (LCP) is an idiopathic osteonecrosis of the femoral head that is most common in children between four and eight years old. The factors that lead to the onset of LCP are still unclear; however, it is believed that interruption of the blood supply to the developing epiphysis is an important factor in the development of the condition. METHODS: Finite element analysis modelling of the blood supply to the juvenile epiphysis was investigated to understand under which circumstances the blood vessels supplying the femoral epiphysis could become obstructed. The identification of these conditions is likely to be important in understanding the biomechanics of LCP. RESULTS: The results support the hypothesis that vascular obstruction to the epiphysis may arise when there is delayed ossification and when articular cartilage has reduced stiffness under compression. CONCLUSION: The findings support the theory of vascular occlusion as being important in the pathophysiology of Perthes disease.Cite this article: M. Pinheiro, C. A. Dobson, D. Perry, M. J. Fagan. New insights into the biomechanics of Legg-Calvé-Perthes' disease: The Role of Epiphyseal Skeletal Immaturity in Vascular Obstruction. Bone Joint Res 2018;7:148-156. DOI: 10.1302/2046-3758.72.BJR-2017-0191.R1.

Three dimensional stereolithography models of cancellous bone structures from muCT data: testing and validation of finite element results.

Stereolithography (STL) models of complex cancellous bone structures have been produced from three-dimensional micro-computed tomography data sets of human cancellous bone histological samples from four skeletal sites. The STL models have been mechanically tested and the derived stiffness compared with that predicted by finite element analysis. The results show a strong correlation (R2 = 0.941) between the predicted and calculated stiffnesses of the structures and show promise for the use of STL as an additional technique to complement the use of finite element models, for the assessment of the mechanical properties of complex cancellous bone structures.

Phytochrome A and Phytochrome B Have Overlapping but Distinct Functions in Arabidopsis Development.

Plant responses to red and far-red light are mediated by a family of photoreceptors called phytochromes. In Arabidopsis thaliana, there are genes encoding at least five phytochromes, and it is of interest to learn if the different phytochromes have overlapping or distinct functions. To address this question for two of the phytochromes in Arabidopsis, we have compared light responses of the wild type with those of a phyA null mutant, a phyB null mutant, and a phyA phyB double mutant. We have found that both phyA and phyB mutants have a deficiency in germination, the phyA mutant in far-red light and the phyB mutant in the dark. Furthermore, the germination defect caused by the phyA mutation in far- red light could be suppressed by a phyB mutation, suggesting that phytochrome B (PHYB) can have an inhibitory as well as a stimulatory effect on germination. In red light, the phyA phyB double mutant, but neither single mutant, had poorly developed cotyledons, as well as reduced red-light induction of CAB gene expression and potentiation of chlorophyll induction. The phyA mutant was deficient in sensing a flowering response inductive photoperiod, suggesting that PHYA participates in sensing daylength. In contrast, the phyB mutant flowered earlier than the wild type (and the phyA mutant) under all photoperiods tested, but responded to an inductive photoperiod. Thus, PHYA and PHYB appear to have complementary functions in controlling germination, seedling development, and flowering. We discuss the implications of these results for possible mechanisms of PHYA and PHYB signal transduction.

New vectors for construction of recombinant high-copy-number yeast acentric-ring plasmids.

Yeast acentric-ring plasmid 1 (YARp1), comprising 1453 bp of entirely yeast chromosomal DNA, is maintained in Saccharomyces cerevisiae as a high-copy, relatively stable plasmid. To determine the feasibility of using YARp1 as a yeast cloning vehicle, we subcloned the GAL1-10 promoter and the URA3 gene into YARp1 at different locations. To facilitate these constructions, a class of permuted YARp1 construction vectors was generated which enabled us to use various restriction sites in YARp1 as insertion points. Transformation frequencies, plasmid stabilities, and copy numbers of these YARp1 derivatives remained elevated, comparable to those of YARp1 itself. Also, when OMP decarboxylase was assayed using strains containing URA3-YARp's, specific activities of 100-300 times that of wild type were found. This evidence supports the use of YARp1 as a high-copy yeast-expression vector or for analyzing structural and regulatory DNA sequences.