Theoretical analysis of the spatio-temporal structure of bone multicellular units

Bone multicellular units (BMUs) maintain the viability of the skeletal tissue by coordinating locally the sequence of bone resorption and bone formation performed by cells of the osteoclastic and osteoblastic lineage. Understanding the emergence and the net bone balance of such structured microsystems out of the complex network of biochemical interactions between bone cells is fundamental for many bone-related diseases and the evaluation of fracture risk. Based on current experimental knowledge, we propose a spatio-temporal continuum model describing the interactions of osteoblastic and osteoclastic cells. We show that this model admits travelling-wave-like solutions with well-confined cell profiles upon specifying external conditions mimicking the environment encountered in cortical bone remodelling. The shapes of the various cell concentration profiles within this travelling structure are intrinsically linked to the parameters of the model such as differentiation, proliferation, and apoptosis rates of bone cells. The internal structure of BMUs is reproduced, allowing for experimental calibration. The spatial distribution of the key regulatory factors can also be exhibited, which in diseased states could give hints as to the biochemical agent most accountable for the disorder

Design of an enquiry-based ‘Practical Only’ course for the teaching of basis skills in first year Biology

First year Biology teaching at the Callaghan Campus of the University of Newcastle has undergone a significant reorganisation in 2006. The rearrangement was conducted with the aims of increasing flexible delivery, improving student learning, reducing overall teaching effort, targeting teaching effort to biology majors and standardising course delivery throughout the university campuses. Key to the reorganisation has been the separation of the practical and lecture components of first year into distinctly separate courses. The practical course runs only in semester 2 and is compulsory for students that intend to graduate with a major in biology. Students that do not intend to continue their biology studies past 1st year are not required nor expected to enrol in the course. Separation of the courses has allowed a renewed focus on basis skills including laboratory and field techniques, the scientific method and practice, report writing and personal interaction. In this paper we present the design of this practical course and explain the process and logic we have used in its construction. Skill acquisition is situated in authentic learning contexts, employing the University campus as a unifying theme. Through an enquiry- based approach, students learn how to think as scientists, posing and testing questions rather than ‘doing the experiment’. The process of building and reinforcing skills (scaffolded learning) and the use of assessment & peer interaction to facilitate the learning process is discussed

Dictionary of medical ethics

Londonxxxi, 459 p.; 22 c

Consent in medicine Convergence and divergence in tradition

SIGLELD:83/30244(Consent) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Theoretical investigation of the role of the RANK–RANKL–OPG system in bone remodeling

The RANK–RANKL–OPG system is an essential signaling pathway involved in bone cell–cell communication, with ample evidence that modification of the RANK–RANKL–OPG signaling pathway has major effects on bone remodeling. The first focus of this paper is to demonstrate that a theoretical model of bone cell–cell interactions is capable of qualitatively reproducing changes in bone associated with RANK–RANKL–OPG signaling. To do this we consider either biological experiments or bone diseases related to receptor and/or ligand deficiencies, including RANKL over-expression, ablation of OPG production and/or RANK receptor modifications. The second focus is to investigate a wide range of possible therapeutic strategies for re-establishing bone homeostasis for various pathologies of the RANK–RANKL–OPG pathway. These simulations indicate that bone diseases associated with the RANK–RANKL–OPG pathway are very effective in triggering bone resorption compared to bone formation. These results align with Hofbauer's “convergence hypothesis”, which states that catabolic bone diseases most effectively act through the RANK–RANKL–OPG system. Additionally, we demonstrate that severity of catabolic bone diseases strongly depends on how many components of this pathway are affected. Using optimization algorithms and the theoretical model, we identify a variety of successful “virtual therapies” for different disease states using both single and dual therapies

Model structure and control of bone remodeling: A theoretical study

It is generally accepted that RANKL is highly expressed in osteoblast precursor cells while OPG is highly expressed in mature osteoblasts, but to date no functional utility to the BMU has been proposed for this particular ligand–decoy–receptor expression profile. As discovered in the mid 90s, the RANK–RANKL–OPG signaling cascade is a major signaling pathway regulating bone remodeling. In this paper we study theoretically the functional implications of particular RANKL/OPG expression profiles on bone volume. For this purpose we formulate an extended bone–cell dynamics model describing functional behaviour of basic multicellular units (BMUs) responsible for bone resorption and formation. This model incorporates the RANK–RANKL–OPG signaling together with the regulating action of TGF-β on bone cells. The bone–cell population model employed here builds on the work of Lemaire et al. (2004) [1], but incorporates the following significant modifications: (i) addition of a rate equation describing changes in bone volume with time as the key ‘output function’ tracking functional behaviour of BMUs, (ii) a rate equation describing release of TGF-β from the bone matrix, (iii) expression of OPG and RANKL on both osteoblastic cell lines, and (iv) modified activator/repressor functions. Using bone volume as a functional selection criterion, we find that there is a preferred arrangement for ligand expression on particular cell types, and further, that this arrangement coincides with biological observations. We then investigate the model parameter space combinatorially, searching for preferred ‘groupings’ of changes in differentiation rates of various cell types. Again, a criterion of bone volume change is employed to identify possible ways of optimally controlling BMU responses. While some combinations of changes in differentiation rates are clearly unrealistic, other combinations of changes in differentiation rates are potentially functionally significant. Most importantly, the combination of parameter changes representing the signaling pathway for TGF-β gives a unique result that appears to have a clear biological rationale. The methodological approach for the investigation of model structure described here offers a theoretical explanation as to why TGF-β has its particular suite of biological effects on bone–cell differentiation rates

Stochastic models for mainland-island metapopulations in static and dynamic landscapes

This paper has three primary aims: to establish an effective means for modelling mainland-island metapopulations inhabiting a dynamic landscape; to investigate the effect of immigration and dynamic changes in habitat on metapopulation patch occupancy dynamics; and to illustrate the implications of our results for decision-making and population management. We first extend the mainland-island metapopulation model of Alonso and McKane [Bull. Math. Biol. 64:913-958, 2002] to incorporate a dynamic landscape. It is shown, for both the static and the dynamic landscape models, that a suitably scaled version of the process converges to a unique deterministic model as the size of the system becomes large. We also establish that, under quite general conditions, the density of occupied patches, and the densities of suitable and occupied patches, for the respective models, have approximate normal distributions. Our results not only provide us with estimates for the means and variances that are valid at all stages in the evolution of the population, but also provide a tool for fitting the models to real metapopulations. We discuss the effect of immigration and habitat dynamics on metapopulations, showing that mainland-like patches heavily influence metapopulation persistence, and we argue for adopting measures to increase connectivity between this large patch and the other island-like patches. We illustrate our results with specific reference to examples of populations of butterfly and the grasshopper Bryodema tuberculata.J. V. Ros