Spinal loads and trunk muscles forces during level walking – A combined in vivo and in silico study on six subjects

During level walking, lumbar spine is subjected to cyclic movements and intricate loading of the spinal discs and trunk musculature. This study aimed to estimate the spinal loads (T12–S1) and trunk muscles forces during a complete gait cycle.Six men, 24–33 years walk barefoot at self-selected speed (4–5 km/h). 3D kinematics and ground reaction forces were recorded using a motion capturing system and two force plates, implemented in an inverse dynamic musculoskeletal model to predict the spinal loads and trunk muscles forces. Additionally, the sensitivity of the intra-abdominal pressure and lumbar segment rotational stiffness was investigated.Peak spinal loads and trunk muscle forces were between the gait instances of heel strike and toe off. In L4–L5 segment, sensitivity analysis showed that average peak compressive, antero-posterior and medio-lateral shear forces were 130–179%, 2–15% and 1–6%, with max standard deviation (±STD) of 40%, 6% and 3% of the body weight. Average peak global muscles forces were 24–55% (longissimus thoracis), 11–23% (iliocostalis thoracis), 12–16% (external oblique), 17–25% (internal oblique) and 0–8% (rectus abdominus) of body weight whereas, the average peak local muscles forces were 11–19% (longissimus lumborum), 14–31% (iliocostalis lumborum) and 12–17% (multifidus). Maximum ± STD of the global and local muscles forces were 13% and 8% of the body weight.Large inter-individual differences were found in peak compressive and trunk muscles forces whereas the sensitivity analysis also showed a substantial variation.     

The N-terminal Proline Hinge Motif Controls the Structure of Bovine Herpesvirus 1-encoded Inhibitor of the Transporter Associated with Antigen Processing Required for its Immunomodulatory Function

Due to unique features, proline residues may control protein structure and function. Here, we investigated the role of ⁵²PPQ⁵⁴ residues, indicated by the recently established experimental 3D structure of bovine herpesvirus 1-encoded UL49.5 protein as forming a characteristic proline hinge motif in its N-terminal domain. UL49.5 acts as a potent inhibitor of the transporter associated with antigen processing (TAP), which alters the antiviral immune response. Mechanisms employed by UL49.5 to affect TAP remain undetermined on a molecular level. We found that mutations in the ⁵²PPQ⁵⁴ region had a vast impact on its immunomodulatory function, increasing cell surface MHC class I expression, TAP levels, and peptide transport efficiency. This inhibitory effect was specific for UL49.5 activity towards TAP but not towards the viral glycoprotein M. To get an insight into the impact of proline hinge modifications on structure and dynamics, we performed all-atom and coarse-grained molecular dynamics studies on the native protein and PPQ mutants. The results demonstrated that the proline hinge sequence with its highly rigid conformation served as an anchor into the membrane. This anchor was responsible for the structural and dynamical behavior of the whole protein, constraining the mobility of the C-terminus, increasing the mobility of the transmembrane region, and controlling the accessibility of the C-terminal residues to the cytoplasmic environment. Those features appear crucial for TAP binding and inhibition. Our findings significantly advance the structural understanding of the UL49.5 protein and its functional regions and support the importance of proline motifs for the protein structure.     

Fatigue Loading Effect in Custom-Made All-on-4 Implants System: A 3D Finite Elements Analysis

ObjectivesThis study aims to evaluate the fatigue stress around custom-made all-on-4 implants system to find out which type of implants have a better performance under different graded multidirectional occlusal forces.Material and methods3D normal and implanted models simulating the “All-on-4” concept were created and analyzed under three different conditions of occlusal loadings. Two types of static and fatigue were applied. Stress distribution was analyzed based on von Mises and Goodman theories in ANSYS environment in addition to the safety factor. Statistical tests were performed to assess the significance of the results as well as the reproducibility of the results.ResultsThe results showed stress increasing reaching a value of 48%, 29% in tilted implants compared to vertical implants and normal cases respectively. In contrast, tilted implants appeared to be less stable (safety factor may reach 0.7) and they may fail during the application of occlusal forces. The safety factor of cortical bone decreased by about 91% in the implanted model compared to the normal model, indicating a higher possibility of bone remodeling around the bone.ConclusionThe orientation and position of occlusal forces had an important influence on stress distribution between the implant and the surrounding bone, and fatigue loading caused greater stresses in comparison with static loading. Lower amounts of stress were found in the vertical implants, ensuring a higher safety factor and a longer clinical service. In contrast, the critical safety factor values are observed in tilted implants, which may fail under the influence of applied occlusal forces.     

Quantification of allochthonous nutrient input into freshwater bodies by herbivorous waterbirds

1. Waterbirds are considered to import large quantities of nutrients to freshwater bodies but quantification of these loadings remains problematic. We developed two general models to calculate such allochthonous nutrient inputs considering food intake, foraging behaviour and digestive performance of waterbirds feeding in terrestrial habitats: an intake model (IM), mainly based on an allometric relationship for energy requirements and a dropping model (DM), based on allometric relationships for defaecation. 2. Reviewed data of nitrogen (N) and phosphorus (P) content of herbivorous food varied according to diet type (foliage, seeds and roots), season and fertilization. For model parameterization average foliage diet contained 38.20 mg N g^?1 and 3.21 mg P g^?1 (dry weight), whereas mean faeces composition was 45.02 mg N g^?1 and 6.18 mg P g^?1. 3. Daily allochthonous nutrient input increased with body mass ranging from 0.29 g N and 0.03 g P in teals Anas crecca to 5.69 g N and 0.57 g P in mute swans Cygnus olor. Results from IM differed from those of DM from ducks to swans by 63–108% for N and by ?4 to 23% for P. Model uncertainty was lowest for the IM and mainly caused by variation in estimates of food retention time (RT). In DM food RT and dropping mass determined model uncertainty in similar extent. 4. Exemplarily applying the models to Dutch wetlands resulted in mean annual contribution of herbivorous waterbirds to allochthonous nutrient loading of 382.8 ± 167.1 tonnes N a^?1and 34.7 ± 2.3 tonnes P a^?1, respectively, which corresponds to annual surface‐water loadings of 1.07 kg N ha^?1 and 0.10 kg P ha^?1. 5. There was a distinct seasonal pattern with peak loadings in January, when bird abundances were highest. Lowest inputs were in August, when bird abundance and nutrient content in food was low and birds foraged less in terrestrial habitats. Three‐quarters of all nutrient input was contributed by greater white‐fronted goose Anser albifrons, greylag goose Anser anser, wigeon Anas penelope and barnacle goose Branta leucopsis alone. 6. We provide general, easy to use calculation methods for the estimation of allochthonous nutrient inputs by waterbirds, which are applicable to a range of waterbird species, a variety of potential diets and feeding behaviours, and across spatial scales. Such tools may greatly assist in the planning and execution of management actions for wetland nutrient budgets.     

Biomechanical evaluation of walking and cycling in children

Physical activity in children is important as it leads to healthy growth due to physiological benefits. However, a physiological benefit can be partially negated by excessive or unphysiological loads within the joints. To gain an initial understanding into this, the present study sought to compare joint loading between walking and cycling in children. With institutional ethical approval, 14 pre-pubertal children aged 8–12 walked on an instrumented treadmill and cycled on a stationary ergometer. Two methods were used to match physiological load. Cardiovascular loads between walking and cycling were matched using heart rate. Metabolic load was normalised by matching estimates of oxygen consumption. Joint reaction forces during cycling and walking as well as joint moments were derived using inverse dynamics. Peak compressive forces were greater on the knees and ankles during walking than during cycling. Peak shear peak forces at the knee and ankle were also significantly larger during walking than during cycling, independent of how physiological load was normalised. For both cycling conditions, ankle moments were significantly smaller during cycling than walking. No differences were found for knee moments. At equivalent physiological intensities, cycling results in less joint loading than walking. It can be speculated that for certain populations and under certain conditions cycling might be a more suitable mode of exercise than weight bearing activities to achieve a given metabolic load.     

Iron content and degree of lipid peroxidation in liver mitochondria isolated from iron-loaded rats

1.The content of non-heme iron and the degree of lipid peroxidation were measured in liver mitochondria isolated from rats injected with either Jectofer (an iron-sorbitol-citric acid complex) or iron-nitrilotriacetate. 2. The sedimentation profiles of the mitochondria from controls and iron-treated rats as revealed by analytical differential centrifugation, indicated single population of mitochondria with $\text{s}{}_{\mathrm{4,B}}$ values of 13200± 560 S and 14200±590 S for controls and iron-loaded animals, respectively. In contrast, the sedimentation profiles of the acid phosphatase activity and the non-heme iron revealed marked polydispersities with at least three populations of particles for both controls and iron-loaded animals. 3. The mitochondria and iron-rich lysosomes were separated by density-gradient centrifugation in an isotonic medium of Percoll and sucrose. With this technique, the amount of non-heme iron in a mitochondrial fraction by differential centrifugation decreased from 69±28 nmol/mg protein to 5.6±1.1 nmol/mg protein and from 19.3±5.6 nmol/mg protein to 3.3±0.6 nmol/mg protein for Jectofer and iron-nitrilotriacetate injected rats, respectively. For control rats the amount of mitochondrial non-heme iron was about 2.7 nmol/mg protein both before and following density gradient centrifugation. The extra amount of non-heme iron still present in the purified mitochondrial fraction from iron-loaded rats, as compared to controls, was further characterized by the reactivity towards bathophenanthroline sulfonate. The results suggest that the extra iron was due to a small amount of either ferritin or hemosiderin still contaminaning the mitochondrial fraction. The amount of mitochondrial heme iron was the same in iron-loaded rats and controls. 4. The degree of lipid peroxidation in the mitochondria was estimated from the amount of malondialdehyde. The thiobarbituric acid method used for the quantitation of malondialdehyde was modified so that it was insensitive to variable amounts of iron present in the samples. No difference in the degree of lipid peroxidation was observed between the mitochondria from iron-loaded rats and controls. 5. In contrast to recent proposals (Hanstein, E.G. et al. (1981) Biochim. Biophys. Acta 678, 293–299), the present study showed that the amounts of non-heme iron and the degrees of lipid peroxidation are the same in mitochondria isolated from iron-loaded and control animals.     

Does gliding when pregnant select for larger females?

For terrestrial vertebrates, gliding imposes unique constraints on the interaction of body mass and structural size, particularly with reference to minimizing wing loading. Females of gliding animals experience increases in wing loading during pregnancy or gravidity, and selection may favour increased structural size to compensate for the added mass. We tested whether pregnant southern flying squirrels Glaucomys volans had similar wing loading as males, and whether females with lower wing loading bore heavier litters, than those with greater wing loading. Males had greater wing loading than females, regardless of the latter's reproductive state (males: 38.4±3.62 N m⁻², pregnant females: 30.7±4.21 N m⁻² and non-pregnant females: 26.8±5.13 N m⁻²). The slope of the linear relationship between planar surface area and body mass was similar between pregnant females and males, however ( F =0.383, P =0.322). Thus female flying squirrels may optimize their litter mass to minimize wing loading during pregnancy. Contrary to our prediction, females with greater wing loading had heavier litters than those with lower wing loading, which suggests reproductive output may be influenced by other ecological factors.     

Dominant role of interface over knee angle for cushioning impact loading and regulating initial leg stiffness

For in vivo impact loadings administered under controlled initial conditions, it was hypothesized that larger initial knee angles (IKA) and softer impacting interfaces would reduce impact loading and initial leg stiffness. A human pendulum was used to deliver controlled impacts to the right foot of 21 subjects for three IKA (0, 20 and 40°) and three interfaces (barefoot, soft and hard EVA foams). The external impact force and the shock experienced by the subjects' shank were measured simultaneously with a wall mounted force platform and a skin mounted accelerometer, respectively. Stiffness of the leg was derived using impact velocity and wall reaction force data. The results disproved the role of the knee joint in regulating initial leg stiffness and provided only partial support for the hypothesized improved cushioning. Larger knee flexion at contact reduced impact force but increased the shock travelling throughout the shank. Conversely, softer interfaces produced sizable reductions in both initial leg stiffness and severity of the impact experienced by the lower limb. Force rate of loading was found to be highly correlated (r=0.95) to limb stiffness that was defined by the heel fat pad and interface deformations. These results would suggest that interface interventions are more likely to protect the locomotor system against impact loading than knee angle strategies.     

Single-Molecule Imaging Reveals the Mechanism Underlying Histone Loading of Schizosaccharomyces pombe AAA+ ATPase Abo1

Chromatin dynamics is essential for maintaining genomic integrity and regulating gene expression. Conserved bromodomain-containing AAA+ ATPases play important roles in nucleosome organization as histone chaperones. Recently, the high-resolution cryo-electron microscopy structures of Schizosaccharomyces pombe Abo1 revealed that it forms a hexameric ring and undergoes a conformational change upon ATP hydrolysis. In addition, single-molecule imaging demonstrated that Abo1 loads H3-H4 histones onto DNA in an ATP hydrolysis-dependent manner. However, the molecular mechanism by which Abo1 loads histones remains unknown. Here, we investigated the details concerning Abo1-mediated histone loading onto DNA and the Abo1-DNA interaction using single-molecule imaging techniques and biochemical assays. We show that Abo1 does not load H2A-H2B histones. Interestingly, Abo1 deposits multiple copies of H3-H4 histones as the DNA length increases and requires at least 80 bp DNA. Unexpectedly, Abo1 weakly binds DNA regardless of ATP, and neither histone nor DNA stimulates the ATP hydrolysis activity of Abo1. Based on our results, we propose an allosteric communication model in which the ATP hydrolysis of Abo1 changes the configuration of histones to facilitate their deposition onto DNA.