David R. Carrier - US grants

9807534 Carrier Vigorous activity requires elevated rates of metabolism. Thus, for an animal to sustain rapid locomotion, it must breathe as it runs. Although humans take breathing during locomotion for granted, there is increasing evidence that the ability to run and breathe at the same time is a derived condition among terrestrial vertebrates. analysis of fishes and amphibians clearly shows that the original function of the muscles of the abdomen and thorax was locomotion rather than lung ventilation. The significance of this is apparent in lizards in which the muscles that produce ventilation also have a role in locomotion. In these lizards, the locomotor function of the axial muscles predominates over their ventilatory function. Consequently, in some species, the locomotor actions of the trunk muscles interfere with breathing to such an extent that and both lung ventilation and oxygen consumption decline as speed increases. Similarly, in dogs, the locomotor function of the axial muscles appears to be dominate over the ventilatory function of these muscles. When trotting dogs uncouple their breathing from the locomotor cycle, activity of all but one or two of the trunk muscles stays locked to the stride cycle. This suggests that tetrapods will either be unable to run and breathe at the same time, or their ventilation must in some way be integrated with their locomotion. The research described in this proposal is intended to increase our understanding of the mechanical linkage between the locomotor and ventilatory systems by investigating the role the axial muscle-skeletal system plays in running and breathing. It has two goals. First Dr. Carrier will use electromyography and manipulation of locomotor forces to test specific hypotheses of locomotor function for the axial muscles in both lizards and mammals. Second, by comparing the intensity of muscle activity when ventilation is coupled versus not coupled to the locomotor cycle, the PI will determine whether locomotor-venti latory coupling decreases the conflict between running and breathing in mammals. This study will contribute to our understanding of the ways in which the oxygen cascade is maintained in the face of conflicting demands resulting from locomotion; and it will help clarify differences between lizards and mammals which may help explain the reliance of running lizards on anaerobic metabolism and the ability of mammals to sustain vigorous locomotion aerobically.

Vertebrate biologists have often studied the axial and appendicular musculoskeletal systems as though they were independent entities. Increasingly, however, evidence is emerging that provides a clear illustration that an atomistic approach to the musculoskeletal system can be misleading. For example, recent attempts to 1) document and understand a possible mechanical constraint on simultaneous running and breathing in ectothermic tetrapods; 2) document the extent to which locomotion interferes with venous return to the heart; 3) unravel the nature and causes of back injury and pain in humans; and 4) identify and test possible locomotor and ventilatory functions of the epaxial and hypaxial muscles have been limited by our understanding of how the extrinsic appendicular muscles load the trunk. If we seek to understand the function and evolution of the vertebrate musculoskeletal system, it is clear that we cannot examine the axial and appendicular systems separately.
The work outlined in this proposal will monitor muscle activity under controlled manipulations of locomotor forces to determine: 1) how the extrinsic muscles of the pectoral and pelvic limbs load the axial musculoskeletal system during steady state locomotion, and 2) how the axial muscles stabilize the trunk against the locomotor loads imposed by the extrinsic appendicular muscles. The rationale of the method is that changes in a particular aspect of the locomotor forces must be met by correlated changes in the recruitment of the muscles responsible for the locomotor force. Hence, correlated changes in locomotor force and muscle recruitment are interpreted to reflect a functional role for the muscle being examined.
At a fundamental level, the information we gain from this work on dogs will be applicable to tetrapods in general and to mammals. First, the basal running gait of tetrapods was a trot. Although there is much variation in body configuration, level of work produced by the axial musculoskeletal system, and integration of running and breathing, the basic mechanics of trotting appear to be largely uniform across tetrapods. Hence, an understanding of the interaction and function of the axial and appendicular muscles of trotting dogs should also provide insight to that of other groups of tetrapods as well. Second, bounding gaits such as the gallop characterize the locomotion of mammals. Improving our understanding of how locomotor forces are transferred between the limbs and trunk and how the trunk is stabilized during galloping in dogs can be expected to provide insight to mammalian body design and locomotion.

During the past 40 years great progress have been made in understanding the functional
basis of anatomical diversity of organisms. More recently, researchers have begun to
unravel the genetic and developmental basis of anatomical structures. To understand
evolutionary transformations, one needs to analyze changes at genetic, developmental, and
phenotypic levels, as well as the integration between these levels. This requires the
construction of genetic, developmental and functional/selectional scenarios. Current
interest focuses on genetic and functional/selectional scenarios. Developmental scenarios
that convincingly link genetic and functional/selectional scenarios are scarce, but see
Beldade et al. 2002 for an example). It is essential to include knowledge of developmental
processes for a continued integration of developmental genetics and morphology. Most
morphological structures develop under the influence of many genes. Therefore, to
comprehend the evolution of the development of these structures, an understanding is
needed of how the involved genes interact, directly or epigenetically, in steering
morphogenetic patterning. The symposium and accompanying contributed paper and poster
sessions will provide a strong stimulus for integrative studies that link developmental
biology, genetics and functional morphology.
Intellectual Merits: There is a wide gap between what is known about the activity of genes
and their role in morphogenesis. Therefore, we perceive an urgent need to facilitate
communication among geneticists, developmental biologists and morphologists. The symposium
and associated activities (contributed paper and poster sessions) will provide important
opportunities for scientists with these two approaches to learn how their different
perspectives and methodologies can be used to broaden interpretations and generate more
robust and testable hypotheses that will shed light on the evolution of vertebrate
structure.
Broader Impacts: The symposium and associated activities (contributed paper and poster
sessions) will be held at the annual meeting of the Society for Integrative and
Comparative Biology, a well-established international meeting that attracts a broad
spectrum of biologists who are interested in interdisciplinary approaches. Symposium
papers will be published in Integrative and Comparative Biology.

Both rapid, economical running and fighting are important in the life histories of most or all terrestrial species. Nevertheless, musculoskeletal "design" that allows rapid, economical running is likely to be incompatible with musculoskeletal design that is appropriate for fighting. This locomotor versus fighting tradeoff may explain many cases of divergence in body form among closely related species and may also help explain why males and females of the same species often differ in the size and proportions of their musculoskeletal system. This study will use comparative methods to test hypotheses of functional tradeoff between specialization for rapid, economical running versus specialization for fighting. The first aim of the investigation is to test a broad set of hypotheses of functional design of the skeletal system in two mammalian orders: Artiodactyla (e.g., deer and antelope) and Carnivora (e.g. wolves and lions). Using museum collections, limb bone proportions will be measured in a large number of species and compared with proxies for male-male aggression (size sexual dimorphism) and maximum running speed. The second and third aims of the study are to quantify sexual differences in the properties of limb bones and muscle architecture in 2 species exhibiting high levels of male-male competition (black bears and bisons) and 2 highly cursorial species (wolves and pronghorns). Hence, this investigation will test hypotheses of functional tradeoff between musculoskeletal specializations for running versus fighting and it will significantly expand our knowledge and understanding of the sexual dimorphism of the mammalian musculoskeletal system. The study will also provide research opportunities for 6 to 9 undergraduate students. We will also create an open access, online library of high resolution CT scans of anatomically aligned cross-sections of the whole limb bones from all of the subjects. Finally, although sexual dimorphism is poorly understood by the general public, it is of broad importance to physiology, evolutionary biology, and human evolution and behavior. We expect the research proposed here to be of general interest and to provide opportunities to educate the public about the biological significance of sexual dimorphism.

This study will examine the characteristics of limbs, muscles and physiology of male mice in order to identify the underlying factors leading to a possible trade-off in locomotion versus physical competition. Locomotion and physical competition are critically important activities for most species. However, anatomical and physiological traits that improve performance in either of these behaviors may impair performance in the other. In socially dominant male house mice, those with greater ability to gain and control territories containing females do so at the cost of less efficient locomotion. This trade-off is likely associated with specific anatomical and physiological traits. The results of this study will increase understanding of animal function and conflicting evolutionary pressures. Additionally, this study will be involved in several public engagement projects, including a science lecture series at correctional institutions in Utah, informal science communications events at the Natural History Museum of Utah, and other programs that bring locally-relevant science to Utah residents. This project will also provide research, presentation, and outreach opportunities for undergraduate students.

This research will investigate underlying factors that influence locomotor economy and physical competitive performance by comparing the following traits in dominant versus non-dominant male mice: 1) skeletal proportions and anatomical mechanical advantages, 2) muscle mass distribution of the trunk and limb muscles, and 3) muscle fiber types of the proximal and distal forelimb and hindlimb using antibody-based histochemistry. These data will be combined with previously collected data on competitive ability in semi-natural enclosures and locomotor economy using open-flow respirometry in a fully enclosed treadmill. Together, these data will allow the identification of which traits at what levels of biological organization underlie the locomotion-competition trade-off. Additionally, because traits that confer the greatest advantage during male-male contests are also typically those that are the most sexually dimorphic, the same hypotheses for differences between dominant and non-dominant males will be applied to male-female differences. This research will help to answer long-standing, unanswered questions at the intersection of natural and sexual selection.

Traumatic brain injury is a leading cause of death and disability in the United States. Over 1.7
million people sustain a brain injury each year and make up one-third of all injuries seen in the
emergency room. Developing rehabilitation and treatment strategies to manage this disease are
important, but preventing the occurrence of brain trauma is also critical component to the solution.
The goal of this proposal is to reduce the risk of traumatic brain injury through smart technology
that collects sensory data to predict and characterize head impact in real-time, optimizes protective
mechanisms based on those impact characteristics, and sends impact trauma attributes to a clinical
database for further analysis and injury risk prediction. This technology will substantially improve
traumatic brain injury prevention and diagnosis in motor vehicle crashes, sports, and industrial
accidents. To accomplish this goal, fundamental research efforts include (1) real-time situational
monitoring to predict when and how dangerous impacts are about to occur and (2) active
prevention mechanisms to reduce the risk of brain injury impact. Initial evaluation of the
technology is in a sports setting, but the system components can be widely adaptive for
implementation in motor vehicles, industrial safety helmets, and living environments for the
elderly.
The research goals of this proposal are to (1) reduce the risk of traumatic brain injury through
advanced situational monitoring, musculoskeletal activation, and impact-specific force reduction;
and (2) to improve potential identification of head injury risk based on multiscale brain
deformation modeling. These goals are accomplished by integrating four fundamental research
efforts. First, tracking and collision detection algorithms are developed based on radio frequency
(RF) sensing, processing, and flexible antenna design. When used in conjunction with triaxial
accelerometers, gyroscopes, and magnetometers, these algorithms provide the sensing capabilities
required to detect objects, capture directional velocity data of surrounding objects, and process
data in real-time to determine probabilities and characteristics of impending collision. Second,
musculoskeletal clenching following auditory warning is investigated as a means of minimizing
head angular acceleration following head or body impact. The development of auditory warning
cues and muscle clench strategies utilizes kinematic musculoskeletal modeling and human subject
studies to identify required auditory cues and response times as well as muscle activation
parameters that best mitigate head angular acceleration during a collision. Third, active force
reduction specific to impending impact characteristics are implemented using a unique controllable
air-filled bladder. Optimal pressure and deflection characteristics of the bladder are based on
impact velocity and direction, and evaluated with a novel three-dimensional multiscale finite
element model of the human head. This model incorporates anatomical variability in the
microstructures at the brain-skull interface, a region that is critical to predictions of head injury.
The fourth fundamental research area uses the multiscale model to investigate the relationship of
head impact force and acceleration to regional deformation of brain tissue upon impact. These
studies will be used to improve predictions of TBI risk from impact kinematics.

This study will examine the characteristics of limbs, muscles and physiology of male mice in order to identify the underlying factors leading to a possible trade-off in locomotion versus physical competition. Locomotion and physical competition are critically important activities for most species. However, anatomical and physiological traits that improve performance in either of these behaviors may impair performance in the other. In socially dominant male house mice, those with greater ability to gain and control territories containing females do so at the cost of less efficient locomotion. This trade-off is likely associated with specific anatomical and physiological traits. The results of this study will increase understanding of animal function and conflicting evolutionary pressures. Additionally, this study will be involved in several public engagement projects, including a science lecture series at correctional institutions in Utah, informal science communications events at the Natural History Museum of Utah, and other programs that bring locally-relevant science to Utah residents. This project will also provide research, presentation, and outreach opportunities for undergraduate students.

This research will investigate underlying factors that influence locomotor economy and physical competitive performance by comparing the following traits in dominant versus non-dominant male mice: 1) skeletal proportions and anatomical mechanical advantages, 2) muscle mass distribution of the trunk and limb muscles, and 3) muscle fiber types of the proximal and distal forelimb and hindlimb using antibody-based histochemistry. These data will be combined with previously collected data on competitive ability in semi-natural enclosures and locomotor economy using open-flow respirometry in a fully enclosed treadmill. Together, these data will allow the identification of which traits at what levels of biological organization underlie the locomotion-competition trade-off. Additionally, because traits that confer the greatest advantage during male-male contests are also typically those that are the most sexually dimorphic, the same hypotheses for differences between dominant and non-dominant males will be applied to male-female differences. This research will help to answer long-standing, unanswered questions at the intersection of natural and sexual selection.