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Nowlan N.C.,Boston University | Nowlan N.C.,EMBL CRG Systems Biology Unit | Jepsen K.J.,Mount Sinai School of Medicine | Morgan E.F.,Boston University
Osteoporosis International | Year: 2011

Summary: We propose a computational model with which to examine the evolution of bone. Our results indicate that changes in subsistence strategy have influenced the evolution of bone growth and mechanoregulation, and predict that bone size, stiffness, and structural strength may decrease in future generations, bringing increased risk of fracture and prevalence of osteoporosis. Introduction: Archeological data suggest that bone size and strength have decreased over evolution. We hypothesize that changing evolutionary pressures and levels of physical activity, both arising from changes in subsistence strategy, have affected the evolution of bone. We propose a computational model with which to examine the evolution of bone growth and mechanoregulation due to the transitions from hunter-gatherer to agricultural to modern lifestyles. Methods: The evolution of genes governing growth and mechanoregulation in a population of bones is simulated, where each individual is represented by a 2-D bone crosssection. Genetic variability is assumed to modulate growth through mechanoregulatory factors that direct periosteal expansion, endosteal expansion/infilling, and ash content accretion in response to strains incurred during walking. Results: The model predicts decreases in cortical area and section modulus (a measure of structural strength) and increases in maximum compressive strain over the course of the simulation, meaning evolution of smaller, less strong, and less stiff bones is predicted for the population average. The model predicts small but continued decreases in size, strength, and stiffness in modern populations, despite the absence of a strong evolutionary advantage to efficient bones during this phase. Conclusion: In conclusion, our results show that changing loading regimes and evolutionary pressures may have influenced the evolution of bone growth and mechanoregulation, and predict that bone size and strength may continue to decrease in future generations, bringing increased risk of fracture and prevalence of osteoporosis. © International Osteoporosis Foundation and National Osteoporosis Foundation 2010. Source


Narendra A.,Australian National University | Reid S.F.,Australian National University | Reid S.F.,EMBL CRG Systems Biology Unit | Raderschall C.A.,Australian National University
PLoS ONE | Year: 2013

Insects face the challenge of navigating to specific goals in both bright sun-lit and dim-lit environments. Both diurnal and nocturnal insects use quite similar navigation strategies. This is despite the signal-to-noise ratio of the navigational cues being poor at low light conditions. To better understand the evolution of nocturnal life, we investigated the navigational efficiency of a nocturnal ant, Myrmecia pyriformis, at different light levels. Workers of M. pyriformis leave the nest individually in a narrow light-window in the evening twilight to forage on nest-specific Eucalyptus trees. The majority of foragers return to the nest in the morning twilight, while few attempt to return to the nest throughout the night. We found that as light levels dropped, ants paused for longer, walked more slowly, the success in finding the nest reduced and their paths became less straight. We found that in both bright and dark conditions ants relied predominantly on visual landmark information for navigation and that landmark guidance became less reliable at low light conditions. It is perhaps due to the poor navigational efficiency at low light levels that the majority of foragers restrict navigational tasks to the twilight periods, where sufficient navigational information is still available. © 2013 Narendra et al. Source


Nowlan N.C.,EMBL CRG Systems Biology Unit | Nowlan N.C.,Trinity College Dublin | Sharpe J.,EMBL CRG Systems Biology Unit | Roddy K.A.,Trinity College Dublin | And 2 more authors.
Birth Defects Research Part C - Embryo Today: Reviews | Year: 2010

A range of clinical conditions in which fetal movement is reduced or prevented can have a severe effect on skeletal development. Animal models have been instrumental to our understanding of the interplay between mechanical forces and skeletal development, particularly the mouse and the chick model systems. In the chick, the most commonly used means of altering the mechanical environment is by pharmaceutical agents which induce paralysis, whereas genetically modified mice with nonfunctional or absent skeletal muscle offer a valuable tool for examining the interplay between muscle forces and skeletogenesis in mammals. This article reviews the body of research on animal models of bone or joint formation in vivo in the presence of an altered or abnormal mechanical environment. In both immobilized chicks and "muscleless limb" mice, a range of effects are seen, such as shorter rudiments with less bone formation, changes in rudiment and joint shape, and abnormal joint cavitation. However, although all bones and synovial joints are affected in immobilized chicks, some rudiments and joints are unaffected in muscleless mice. We propose that extrinsic mechanical forces from movements of the mother or littermates impact on skeletogenesis in mammals, whereas the chick embryo is reliant on intrinsic movement for mechanical stimulation. The insights gained from animal models into the mechanobiology of embryonic skeletal development could provide valuable cues to prospective tissue engineers of cartilage and bone and contribute to new or improved treatments to minimize the impact on skeletal development of reduced movement in utero. © 2010 Wiley-Liss, Inc. Source


Saias L.,Center for Genomic Regulation | Saias L.,University Pompeu Fabra | Swoger J.,University Pompeu Fabra | Swoger J.,EMBL CRG Systems Biology Unit | And 11 more authors.
Developmental Cell | Year: 2015

Biological tissues must generate forces to shape organs and achieve proper development. Such forces often result from the contraction of an apical acto-myosin meshwork. Here we describe an alternative mechanism for tissue contraction, based on individual cell volume change. We show that during Drosophila dorsal closure (DC), a wound healing-related process, the contraction of the amnioserosa (AS) is associated with a major reduction of the volume of its cells, triggered by caspase activation at the onset of the apoptotic program of AS cells. Cell volume decrease results in a contractile force that promotes tissue shrinkage. Estimating mechanical tensions with laser dissection and using 3D biophysical modeling, we show that the cell volume decrease acts together with the contraction of the actin cable surrounding the tissue to govern DC kinetics. Our study identifies a mechanism by which tissues generate forces and movements by modulating individual cell volume during development. © 2015 Elsevier Inc. Source


Gomez-Marin A.,EMBL CRG Systems Biology Unit | Stephens G.J.,Princeton University | Louis M.,EMBL CRG Systems Biology Unit
Nature Communications | Year: 2011

The ability to respond to chemical stimuli is fundamental to the survival of motile organisms, but the strategies underlying odour tracking remain poorly understood. Here we show that chemotaxis in Drosophila melanogaster larvae is an active sampling process analogous to sniffing in vertebrates. Combining computer-vision algorithms with reconstructed olfactory environments, we establish that larvae orient in odour gradients through a sequential organization of stereotypical behaviours, including runs, stops, lateral head casts and directed turns. Negative gradients, integrated during runs, control the timing of turns. Positive gradients detected through high-amplitude head casts determine the direction of individual turns. By genetically manipulating the peripheral olfactory circuit, we examine how orientation adapts to losses and gains of function in olfactory input. Our findings suggest that larval chemotaxis represents an intermediate navigation strategy between the biased random walks of Escherichia Coli and the stereo-olfaction observed in rats and humans. © 2011 Macmillan Publishers Limited. All rights reserved. Source

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