Mechanotransduction in intervertebral discs

Mechanotransduction plays a critical role in intracellular functioning—it allows cells to translate external physical forces into internal biochemical activities, thereby affecting processes ranging from proliferation and apoptosis to gene expression and protein synthesis in a complex web of interactions and reactions. Accordingly, aberrant mechanotransduction can either lead to, or be a result of, a variety of diseases or degenerative states. In this review, we provide an overview of mechanotransduction in the context of intervertebral discs, with a focus on the latest methods of investigating mechanotransduction and the most recent findings regarding the means and effects of mechanotransduction in healthy and degenerative discs. We also provide some discussion of potential directions for future research and treatments.     

Numerical simulation of cross-country skiing

A program for numerical simulation of a whole ski race, from start to finish, is developed in MATLAB. The track is modelled by a set of cubical splines in two dimensions and can be used to simulate a track in a closed loop or with the start and finish at different locations. The forces considered in the simulations are gravitational force, normal force between snow and skis, drag force from the wind, frictional force between snow and ski and driving force from the skier. The differential equations of motion are solved from start to finish with the Runge–Kutta method. Different wind situations during the race can be modelled, as well as different glide conditions on different parts of the track. It is also possible to vary the available power during the race. The simulation program's output is the total time of the race, together with the forces and speed during different parts of the race and intermediate times at selected points. Some preliminary simulations are also presented.     

Inquiring into Familiar Objects: An Inquiry-Based Approach to Introduce Scientific Vocabulary

Learning science vocabulary is an often tedious but important component of many curricula. Frequently, students are expected to learn science vocabulary indirectly, but this method can hinder the success of lower-performing students (Carlisle, Fleming, and Gudbrandsen 2000). We have developed an inquiry-based vocabulary activity wherein students explore how new words apply to familiar objects, piquing their interest in the words’ meanings, prior to direct instruction. Groups of students were asked to apply new vocabulary words to familiar objects set up at various rotation stations. The students were encouraged to play with the objects, discuss answers with their group, and write down the vocabulary words they thought best described each object. Since the words were new to the students, there was no credit for correct answers, making the students comfortable exploring a new topic. After the rotation stations, we led students in a discussion of their answers and followed up with direct instruction on the words’ definitions. Here we give three examples of this activity used in our physical science classroom—one each for energy, simple machines, and force vocabulary—but this activity can easily be modified for biology and Earth science curricula.     

Intermolecular electrostatics via molecular fragmentation: an application to crystal structure prediction

Molecular fragmentation is an attractive approach to the simulation of large molecules, in which calculations are carried out on small segments of the molecule, achieving linear scaling but reduced accuracy. Its application to crystal structure prediction (CSP) is challenged by high accuracy requirements. In this study, the applicability of a fragmentation scheme is tested for distributed multipoles, which are used in CSP to model intermolecular electrostatic interactions. Four test systems are investigated: a molecular salt, the highly conjugated molecule retinal, a model pharmaceutical molecule and the nonlinear molecule nitrotriacetanilide. It is demonstrated that fragment-based electrostatics reproduce, to an acceptable degree, a set of crystal structures generated using whole-molecule electrostatics. Inclusion of the molecular environment of each fragment out to four bonds separation is found to provide a sufficiently accurate set of distributed multipoles for the purposes of CSP.     

ECM concentration and cell-mediated traction forces play a role in vascular network assembly in 3D bioprinted tissue

Tissue vascularization is critical to enable oxygen and nutrient supply. Therefore, establishing expedient vasculature is necessary for the survival of tissue after transplantation. The use of biomechanical forces, such as cell-induced traction forces, may be a promising method to encourage growth of the vascular network. Three-dimensional (3D) bioprinting, which offers unprecedented versatility through precise control over spatial distribution and structure of tissue constructs, can be used to generate capillary-like structures in vitro that would mimic microvessels. This study aimed to develop an in vitro, 3D bioprinted tissue model to study the effect of cellular forces on the spatial organization of vascular structures and tissue maturation. The developed in vitro model consists of a 3D bioprinted polycaprolactone (PCL) frame with a gelatin spacer hydrogel layer and a gelatin–fibrin–hyaluronic acid hydrogel layer containing normal human dermal fibroblasts and human umbilical vein endothelial cells printed as vessel lines on top. The formation of vessel-like networks and vessel lumens in the 3D bioprinted in vitro model was assessed at different fibrinogen concentrations with and without inhibitors of cell-mediated traction forces. Constructs containing 5 mg/ml fibrinogen had longer vessels compared to the other concentrations of fibrinogen used. Also, for all concentrations of fibrinogen used, most of the vessel-like structures grew parallel to the direction the PCL frame-mediated tensile forces, with very few branching structures observed. Treatment of the 3D bioprinted constructs with traction inhibitors resulted in a significant reduction in length of vessel-like networks. The 3D bioprinted constructs also had better lumen formation, increased collagen deposition, more elaborate actin networks, and well-aligned matrix fibers due to the increased cell-mediated traction forces present compared to the non-anchored, floating control constructs. This study showed that cell traction forces from the actomyosin complex are critical for vascular network assembly in 3D bioprinted tissue. Strategies involving the use of cell-mediated traction forces may be promising for the development of bioprinting approaches for fabrication of vascularized tissue constructs.     

In vivo hip joint loads and pedal forces during ergometer cycling

The rising prevalence of osteoarthritis and an increase in total hip replacements calls for attention to potential therapeutic activities. Cycling is considered as a low impact exercise for the hip joint and hence recommended. However, there are limited data about hip joint loading to support this claim. The aim of this study was to measure synchronously the in vivo hip joint loads and pedal forces during cycling. The in vivo hip joint loads were measured in 5 patients with instrumented hip implants. Data were collected at several combinations of power and cadence, at two saddle heights.Joint loads and pedal forces showed strong linear correlation with power. So the relationship between the external pedal forces and internal joint forces was shown. While cycling at different cadences the minimum joint loads were acquired at 60 RPM. The lower saddle height configuration results in an approximately 15% increase compared to normal saddle height.The results offered new insights into the actual effects of cycling on the hip joint and can serve as useful tools while developing an optimum cycling regimen for individuals with coxarthrosis or following total hip arthroplasty. Due to the relatively low contact forces, cycling at a moderate power level of 90 W at a normal saddle height is suitable for patients.     

Host plant nutritional quality affects the performance of the parasitoid Diadegma insulare

The well documented biochemical profile of Brassicaceae, oligophagy of the herbivore Plutella xylostella (L.) (Lepidoptera: Plutellidae), and host specialization of the parasitoid Diadegma insulare (Cresson) (Hymenoptera: Ichneumonidae) provide an ideal system for investigating tritrophic interactions mediated by nutritional quality of plants. We evaluated the bottom-up effects of five soil fertility regimes on nutritional quality of canola (Brassica napus L.) and then on several fitness correlates of female and male D. insulare as mediated through P. xylostella. Variation in soil fertility influenced the nutritional quality of host plants and this in turn affected the performance of D. insulare. In general, D. insulare performed best on plants grown with 3.0 g fertilizer pot⁻¹; these plants had 2.06-, 3.77-, and 1.02-fold more nitrogen, phosphorous and potassium, respectively than ones grown without any added fertilizer. P. xylostella escape from D. insulare was highest (32%) on plants grown at 1.0 g fertilizer, and this could be attributed to both physical and physiological defense mechanisms mediated by host plant nutritional quality. Plant stress and plant vigor are competing paradigms pertaining to the performance of herbivorous insects on their host plants. These hypotheses were originally proposed to predict responses of herbivores, but may also explain the effects of plant quality on koinobiont parasitoids, such as D. insulare.     

In-stent graft helical flow intensity reduces the risk of migration after endovascular aortic repair

During the last years endovascular aneurysm repair (EVAR) became the elective treatment for abdominal aortic aneurysms (AAAs) thanks to lower mortality and morbidity rates than open surgery. In face of these advantages, stent-graft performances are still clinically suboptimal. In particular, post-surgical complications derive from device migration as a consequence of the hemodynamic forces acting on the endograft. In this regard, while the importance of hemodynamic surface forces is well recognized, the role of the in-stent flow is still unclear. Here we hypothesize that in-stent helical blood flow patterns might influence the distribution of the displacement forces (DFs) acting on the stent-graft and, ultimately, the risk of stent migration. To test this hypothesis, the hemodynamics of 20 post-EVAR models of patients treated with two different commercial endografts was analyzed using computational hemodynamics.The main findings of the study indicate that: (1) helical flow intensity decreases the risk of endograft migration, as given by an inverse correlation between helicity intensity (h₂) and time-averaged displacement forces (TADFs) (p < 0.05); (2) unbalanced counter-rotating helical structures in the legs of the device contribute, in particular along the systole, to significantly suppress TADFs (p < 0.01); (3) as expected, helical flow intensity is positively correlated with pressure drop and resistance to flow (p < 0.001). The findings of this study suggest that a design strategy promoting in-stent helical flow structures could contribute to minimize the risk of migration of implanted EVAR devices.