Tumours are known as wounds that do not heal - this implies that cells that are involved in angiogenesis and the response to injury, such as endothelial cells and fibroblasts, have a prominent role in the progression, growth and spread of cancers. Fibroblasts are associated with cancer cells at all stages of cancer progression, and their structural and functional contributions to this process are beginning to emerge. Their production of growth factors, chemokines and extracellular matrix facilitates the angiogenic recruitment of endothelial cells and pericytes. Fibroblasts are therefore a key determinant in the malignant progression of cancer and represent an important target for cancer therapies.

Fibroblasts in cancer

Dynamic simulations of movement allow one to study neuromuscular coordination, analyze athletic performance, and estimate internal loading of the musculoskeletal system. Simulations can also be used to identify the sources of pathological movement and establish a scientific basis for treatment planning. We have developed a freely available, open-source software system (OpenSim) that lets users develop models of musculoskeletal structures and create dynamic simulations of a wide variety of movements. We are using this system to simulate the dynamics of individuals with pathological gait and to explore the biomechanical effects of treatments. OpenSim provides a platform on which the biomechanics community can build a library of simulations that can be exchanged, tested, analyzed, and improved through a multi-institutional collaboration. Developing software that enables a concerted effort from many investigators poses technical and sociological challenges. Meeting those challenges will accelerate the discovery of principles that govern movement control and improve treatments for individuals with movement pathologies.

/pdf/opensim-open-source-software-to-create-and-analyze-dynamic-363rij3wr7.pdf

OpenSim: Open-Source Software to Create and Analyze Dynamic Simulations of Movement

The Insects has been the standard textbook in the field since the first edition published over forty years ago. Building on the strengths of Chapman's original text, this long-awaited 5th edition has been revised and expanded by a team of eminent insect physiologists, bringing it fully up-to-date for the molecular era. The chapters retain the successful structure of the earlier editions, focusing on particular functional systems rather than taxonomic groups and making it easy for students to delve into topics without extensive knowledge of taxonomy. The focus is on form and function, bringing together basic anatomy and physiology and examining how these relate to behaviour. This, combined with nearly 600 clear illustrations, provides a comprehensive understanding of how insects work. Now also featuring a richly illustrated prologue by George McGavin, this is an essential text for students, researchers and applied entomologists alike.

The insects: structure and function.

Mechanical stresses were applied directly to cell surface receptors with a magnetic twisting device. The extracellular matrix receptor, integrin beta 1, induced focal adhesion formation and supported a force-dependent stiffening response, whereas nonadhesion receptors did not. The cytoskeletal stiffness (ratio of stress to strain) increased in direct proportion to the applied stress and required intact microtubules and intermediate filaments as well as microfilaments. Tensegrity models that incorporate mechanically interdependent struts and strings that reorient globally in response to a localized stress mimicked this response. These results suggest that integrins act as mechanoreceptors and transmit mechanical signals to the cytoskeleton. Mechanotransduction, in turn, may be mediated simultaneously at multiple locations inside the cell through force-induced rearrangements within a tensionally integrated cytoskeleton.

https://science.sciencemag.org/content/sci/260/5111/1124.full.pdf

Mechanotransduction across the cell surface and through the cytoskeleton

The survival and well-being of all species requires appropriate physiological responses to environmental and homeostatic challenges. The re-establishment and maintenance of homeostasis entails the coordinated activation and control of neuroendocrine and autonomic stress systems. These collective stress responses are mediated by largely overlapping circuits in the limbic forebrain, the hypothalamus and the brainstem, so that the respective contributions of the neuroendocrine and autonomic systems are tuned in accordance with stressor modality and intensity. Limbic regions that are responsible for regulating stress responses intersect with circuits that are responsible for memory and reward, providing a means to tailor the stress response with respect to prior experience and anticipated outcomes.

Neural regulation of endocrine and autonomic stress responses.

Cardiac fibroblasts form one of the largest cell populations, in terms of cell numbers, in the heart They contribute to structural, biochemical, mechanical and electrical properties of the myocardium Nonetheless, they are often disregarded by in vivo and in vitro studies into cardiac function This review summarizes our understanding of fibroblast origin and identity, their structural organization and role in myocardial architecture, as well as functional aspects related to cell signalling and electro-mechanical function in the heart

/pdf/structural-and-functional-characterisation-of-cardiac-2xqu02iupj.pdf

Structural and functional characterisation of cardiac fibroblasts

Cardiac fibroblasts, myocytes, endothelial cells, and vascular smooth muscle cells are the major cellular constituents of the heart. The aim of this study was to observe alterations in myocardial c...

Determination of cell types and numbers during cardiac development in the neonatal and adult rat and mouse.

The Physiome Project will provide a framework for modelling the human body, using computational methods that incorporate biochemical, biophysical and anatomical information on cells, tissues and organs. The main project goals are to use computational modelling to analyse integrative biological function and to provide a system for hypothesis testing.

Integration from proteins to organs: the Physiome Project.

The collagen network of the heart

—Extracellular matrix provides a structural, chemical, and mechanical substrate that is essential in cardiac development, growth, and responses to pathophysiological signals. Transmembrane receptors termed integrins provide a dynamic interaction of environmental cues and intracellular events. Integrins orchestrate multiple functions in the intact organism including organogenesis, regulation of gene expression, cell proliferation, differentiation, migration, and death. They are expressed in all cellular components of the cardiovascular system, including the vasculature, blood, cardiac myocytes and nonmuscle cardiac cells. The focus of this review will be on the role of integrins in the myocardium. We will provide background on integrin structure and function, discuss how the expression of integrins is critical to the form and function of the developing and postnatal myocardium, and review the known data on integrins as signaling molecules in the heart. Finally, we will offer insights to the future ...

Thomas K. Borg

Papers

Structural and functional characterisation of cardiac fibroblasts

Determination of cell types and numbers during cardiac development in the neonatal and adult rat and mouse.

Integration from proteins to organs: the Physiome Project.

The collagen network of the heart

Integrins and the Myocardium