Polarized cortical tension drives zebrafish epiboly movements

The principles underlying the biomechanics of morphogenesis are largely unknown. Epiboly is an essential embryonic event in which three tissues coordinate to direct the expansion of the blastoderm. How and where forces are generated during epiboly, and how these are globally coupled remains elusive. Here we developed a method, hydrodynamic regression (HR), to infer 3D pressure fields, mechanical power, and cortical surface tension profiles. HR is based on velocity measurements retrieved from 2D+T microscopy and their hydrodynamic modeling. We applied HR to identify biomechanically active structures and changes in cortex local tension during epiboly in zebrafish. Based on our results, we propose a novel physical description for epiboly, where tissue movements are directed by a polarized gradient of cortical tension. We found that this gradient relies on local contractile forces at the cortex, differences in elastic properties between cortex components and the passive transmission of forces within the yolk cell. All in all, our work identifies a novel way to physically regulate concerted cellular movements that might be instrumental for the mechanical control of many morphogenetic processes.Peer ReviewedPostprint (author's final draft

Process of discovery: A fourth-year translational science course

The Liaison Committee on Medical Education notes the importance of educating medical students on clinical and translational research principles.To describe a fourth-year course, “Process of discovery,” which addresses teaching these principles, and to discuss students’ perceptions of the course.Core components and pedagogical methods of this course are presented. Course assessment was performed with specific pre- and post-course assessments.During academic years 2004 to 2009, 562 students were enrolled, with assessment response rate of 94% pre-course and 85% post-course. The students’ self-assessment of their current understanding of clinical and translation research significantly increased, as well as their understanding of how clinical advances will take place over the next decade.A fourth-year course teaching clinical and translational research is successful, is seen as a positive experience and can meet the requirements for including clinical and translational research in the medical school curriculum

Incorporating chemical signalling factors into cell-based models of growing epithelial tissues

In this paper we present a comprehensive computational framework within which the effects of chemical signalling factors on growing epithelial tissues can be studied. The method incorporates a vertex-based cell model, in conjunction with a solver for the governing chemical equations. The vertex model provides a natural mesh for the finite element method (FEM), with node movements determined by force laws. The arbitrary Lagrangian–Eulerian formulation is adopted to account for domain movement between iterations. The effects of cell proliferation and junctional rearrangements on the mesh are also examined. By implementing refinements of the mesh we show that the finite element (FE) approximation converges towards an accurate numerical solution. The potential utility of the system is demonstrated in the context of Decapentaplegic (Dpp), a morphogen which plays a crucial role in development of the Drosophila imaginal wing disc. Despite the presence of a Dpp gradient, growth is uniform across the wing disc. We make the growth rate of cells dependent on Dpp concentration and show that the number of proliferation events increases in regions of high concentration. This allows hypotheses regarding mechanisms of growth control to be rigorously tested. The method we describe may be adapted to a range of potential application areas, and to other cell-based models with designated node movements, to accurately probe the role of morphogens in epithelial tissues

Study on Multicellular Systems Using a Phase Field Model

A model of multicellular systems with several types of cells is developed from the phase field model. The model is presented as a set of partial differential equations of the field variables, each of which expresses the shape of one cell. The dynamics of each cell is based on the criteria for minimizing the surface area and retaining a certain volume. The effects of cell adhesion and excluded volume are also taken into account. The proposed model can be used to find the position of the membrane and/or the cortex of each cell without the need to adopt extra variables. This model is suitable for numerical simulations of a system having a large number of cells. The two-dimensional results of cell adhesion, rearrangement of a cell cluster, and chemotaxis as well as the three-dimensional results of cell clusters on the substrate are presented.Comment: 13 pages, 7 figure

Relationship Between Peer Assessment During Medical School, Dean’s Letter Rankings, and Ratings by Internship Directors

BACKGROUND: It is not known to what extent the dean’s letter (medical student performance evaluation [MSPE]) reflects peer-assessed work habits (WH) skills and/or interpersonal attributes (IA) of students. OBJECTIVE: To compare peer ratings of WH and IA of second- and third-year medical students with later MSPE rankings and ratings by internship program directors. DESIGN AND PARTICIPANTS: Participants were 281 medical students from the classes of 2004, 2005, and 2006 at a private medical school in the northeastern United States, who had participated in peer assessment exercises in the second and third years of medical school. For students from the class of 2004, we also compared peer assessment data against later evaluations obtained from internship program directors. RESULTS: Peer-assessed WH were predictive of later MSPE groups in both the second (F = 44.90, P < .001) and third years (F = 29.54, P < .001) of medical school. Interpersonal attributes were not related to MSPE rankings in either year. MSPE rankings for a majority of students were predictable from peer-assessed WH scores. Internship directors’ ratings were significantly related to second- and third-year peer-assessed WH scores (r = .32 [P = .15] and r = .43 [P = .004]), respectively, but not to peer-assessed IA. CONCLUSIONS: Peer assessment of WH, as early as the second year of medical school, can predict later MSPE rankings and internship performance. Although peer-assessed IA can be measured reliably, they are unrelated to either outcome

Coordinated optimization of visual cortical maps (I) Symmetry-based analysis

In the primary visual cortex of primates and carnivores, functional architecture can be characterized by maps of various stimulus features such as orientation preference (OP), ocular dominance (OD), and spatial frequency. It is a long-standing question in theoretical neuroscience whether the observed maps should be interpreted as optima of a specific energy functional that summarizes the design principles of cortical functional architecture. A rigorous evaluation of this optimization hypothesis is particularly demanded by recent evidence that the functional architecture of OP columns precisely follows species invariant quantitative laws. Because it would be desirable to infer the form of such an optimization principle from the biological data, the optimization approach to explain cortical functional architecture raises the following questions: i) What are the genuine ground states of candidate energy functionals and how can they be calculated with precision and rigor? ii) How do differences in candidate optimization principles impact on the predicted map structure and conversely what can be learned about an hypothetical underlying optimization principle from observations on map structure? iii) Is there a way to analyze the coordinated organization of cortical maps predicted by optimization principles in general? To answer these questions we developed a general dynamical systems approach to the combined optimization of visual cortical maps of OP and another scalar feature such as OD or spatial frequency preference.Comment: 90 pages, 16 figure

Chaste: an open source C++ library for computational physiology and biology

Chaste - Cancer, Heart And Soft Tissue Environment - is an open source C++ library for the computational simulation of mathematical models developed for physiology and biology. Code development has been driven by two initial applications: cardiac electrophysiology and cancer development. A large number of cardiac electrophysiology studies have been enabled and performed, including high performance computational investigations of defibrillation on realistic human cardiac geometries. New models for the initiation and growth of tumours have been developed. In particular, cell-based simulations have provided novel insight into the role of stem cells in the colorectal crypt. Chaste is constantly evolving and is now being applied to a far wider range of problems. The code provides modules for handling common scientific computing components, such as meshes and solvers for ordinary and partial differential equations (ODEs/PDEs). Re-use of these components avoids the need for researchers to "re-invent the wheel" with each new project, accelerating the rate of progress in new applications. Chaste is developed using industrially-derived techniques, in particular test-driven development, to ensure code quality, re-use and reliability. In this article we provide examples that illustrate the types of problems Chaste can be used to solve, which can be run on a desktop computer. We highlight some scientific studies that have used or are using Chaste, and the insights they have provided. The source code, both for specific releases and the development version, is available to download under an open source Berkeley Software Distribution (BSD) licence at http://www.cs.ox.ac.uk/chaste, together with details of a mailing list and links to documentation and tutorials