Only the Good Die Old? Ontogenetic Determinants of Locomotor Performance in Eastern Cottontail Rabbits (Sylvilagus floridanus).

For many animals, the juvenile stage of life can be particularly perilous. Once independent, immature animals must often complete the same basic survival functions as adults despite smaller body size and other growth-related limits on performance. Because, by definition, juveniles have yet to reproduce, we should expect strong selection for mechanisms to offset these ontogenetic limitations, allowing individuals to reach reproductive adulthood and maintain Darwinian fitness. We use an integrated ontogenetic dataset on morphology, locomotor performance, and longevity in wild cottontail rabbits (Sylvilagus floridanus, Allen 1848) to test the hypothesis that prey animals are under selective pressure to maximize juvenile performance. We predicted that (1) juveniles would accelerate more quickly than adults, allowing them to reach adult-like escape speeds, and (2) juveniles with greater levels of performance should survive for longer durations in the wild, thus increasing their reproductive potential. Using high-speed video and force platform measurements, we quantified burst acceleration, escape speed, and mechanical power production in 38 wild-caught S. floridanus (26 juveniles, 12 adults; all rabbits >1 kg in body mass were designated to be adults, based on published growth curves and evidence of epiphyseal fusion). A subsample of 22 rabbits (15 juveniles, 7 adults) was fitted with radio-telemetry collars for documenting survivorship in the wild. We found that acceleration and escape speed peaked in the late juvenile period in S. floridanus, at an age range that coincides with a period of pronounced demographic attrition in wild populations. Differences in mass-specific mechanical power production explained ∼75% of the variation in acceleration across the dataset, indicating that juvenile rabbits outpace adults by producing more power per unit body mass. We found a positive, though non-significant, association between peak escape speed and survivorship duration in the wild, suggesting a complex relationship between locomotor performance and fitness in growing S. floridanus.

Off-Label Use of Intravenous Immunoglobulin with Methylprednisolone to Treat Parsonage-Turner Syndrome in a United States Marine.

Neuralgic amyotrophy (NA) also known as Parsonage-Turner syndrome is an inflammatory disorder of the brachial plexus characterized by sudden, acute onset of severe pain of the arm and/or shoulder followed by muscle weakness and sensory abnormalities. Although management may involve physical therapy, immunomodulatory drugs, and analgesics, there is nothing specific for the treatment of NA. Full functional recovery can take months to years, but recurrence and/or persistence of symptoms and disability are frequent. This case reports a 22-year-old male who recovered from NA within 3 months following treatment with 1000 mg of methylprednisolone and off-label use of 0.5 g/kg of intravenous immunoglobulins (IVIG) for four consecutive days. Three years later, the patient experienced soreness and paresthesia of the shoulder following a military shooting exercise, and 0.75 g/kg of IVIG and 1000 mg of MP were prescribed for 2 consecutive days resulting in complete recovery and no recurrences to date. EMG findings, 3.5-year postinitial treatment, revealed improvement in the brachial plexopathy. This provides support for the combined use of IVIG and glucocorticoids in the treatment of NA and highlights the need for further studies investigating whether this combined treatment regimen may accelerate recovery and improve long-term outcomes for patients diagnosed with NA.

Response of the Axial Skeleton to Bipedal Loading Behaviors in an Experimental Animal Model.

Many derived aspects of modern human axial skeletal morphology reflect our reliance on obligate bipedal locomotion. Insight into the adaptive significance of features, particularly in the spine, has been gained through experimental studies that induce bipedal standing or walking in quadrupedal mammals. Using an experimental animal model (Rattus norvegicus), the present study builds on earlier work by incorporating additional metrics of the cranium, employing quantitative methods established in the paleoanthropological literature, and exploring how variation in mechanical loading regimes impacts axial anatomy. Rats were assigned to one of five experimental groups, including "fully loaded bipedal walking," "partially loaded bipedal walking," "standing bipedally," "quadrupedal walking," and "no exercise control," and engaged in the behavior over 12-weeks. From µCT data obtained at the beginning and end of the experiment, we measured foramen magnum position and orientation, lumbar vertebral body wedging, cranial surface area of the lumbar and first sacral vertebral bodies, and sacral mediolateral width. Results demonstrate that bipedal rodents generally have more anteriorly positioned foramina magna, more dorsally wedged lumbar vertebrae, greater articular surface areas of lumbar and first sacral vertebral bodies, and sacra that exhibit greater mediolateral widths, compared to quadrupedal rodents. We further document variation among bipedal loading behavior groups (e.g., bipedal standing vs. walking). Our experimental animal model reveals how loading behaviors and adaptations may be specifically linked, and implicates a potential role for developmental plasticity in the evolutionary acquisition of bipedal adaptations in the hominin lineage. Anat Rec, 2018. © 2018 American Association for Anatomy.

Ontogeny of effective mechanical advantage in eastern cottontail rabbits (Sylvilagus floridanus).

Juvenile animals must survive in the same environment as adults despite smaller sizes, immature musculoskeletal tissues, general ecological naïveté and other limits of performance. Developmental changes in muscle leverage could constitute one mechanism to promote increased performance in juveniles despite ontogenetic limitations. We tested this hypothesis using a holistic dataset on growth and locomotor development in wild eastern cottontail rabbits (Sylvilagus floridanus) to examine ontogenetic changes in hindlimb muscle effective mechanical advantage (EMA). EMA is a dimensionless index of muscle leverage, equal to the quotient of average muscle lever length and the load arm length of the ground reaction force (GRF), effectively representing the magnitude of output force arising from a given muscle force. We found that EMA at the hip and ankle joints, as well as overall hindlimb EMA, significantly declined across ontogeny in S. floridanus, whereas EMA at the knee joint remained unchanged. Ontogenetic decreases in EMA were due to isometric scaling of muscle lever arm lengths alongside positive ontogenetic allometry of GRF load arm lengths - which in turn was primarily related to positive allometry of hindlimb segment lengths. Greater EMA limits the estimated volume of hindlimb extensor muscle that has to be activated in young rabbits, likely mitigating the energetic cost of locomotion and saving metabolic resources for other physiological functions, such as growth and tissue differentiation. An additional examination of limb growth allometry across a diverse sample of mammalian taxa suggests that ontogenetic decreases in limb joint EMA may be a common mammalian trend.

The impact of bipedal mechanical loading history on longitudinal long bone growth.

Longitudinal bone growth is accomplished through a process where proliferating chondrocytes produce cartilage in the growth plate, which ultimately ossifies. Environmental influences, like mechanical loading, can moderate the growth of this cartilage, which can alter bone length. However, little is known about how specific behaviors like bipedalism, which is characterized by a shift in body mass (mechanical load), to the lower limbs, may impact bone growth. This study uses an experimental approach to induce bipedal behaviors in a rodent model (Rattus norvegicus) over a 12-week period using a treadmill-mounted harness system to test how rat hindlimbs respond to the following loading conditions: 1) fully loaded bipedal walking, 2) partially loaded bipedal walking, 3) standing, 4) quadrupedal walking, and 5) no exercise control. These experimental conditions test whether mechanical loading from 1) locomotor or postural behaviors, and 2) a change in the magnitude of load can moderate longitudinal bone growth in the femur and tibia, relative to controls. The results demonstrate that fully loaded bipedal walking and bipedal standing groups showed significant differences in the percentage change in length for the tibia and femur. When comparing the change from baseline, which control for body mass, all bipedal groups showed significant differences in tibia length compared to control groups. However, there were no absolute differences in bone length, which suggests that mechanical loads from bipedal behaviors may instead be moderating changes in growth velocity. Implications for the relationship between bipedal behaviors and longitudinal bone growth are discussed.

An ontogenetic framework linking locomotion and trabecular bone architecture with applications for reconstructing hominin life history.

The ontogeny of bipedal walking is considered uniquely challenging, due in part to the balance requirements of single limb support. Thus, locomotor development in humans and our bipedal ancestors may track developmental milestones including the maturation of the neuromuscular control system. Here, we examined the ontogeny of locomotor mechanics in children aged 1-8, and bone growth and development in an age-matched skeletal sample to identify bony markers of locomotor development. We show that step-to-step variation in mediolateral tibia angle relative to the vertical decreases with age, an indication that older children increase stability. Analyses of trabecular bone architecture in the distal tibia of an age-matched skeletal sample (the Norris Farms #36 archaeological skeletal collection) show a bony signal of this shift in locomotor stability. Using a grid of eleven cubic volumes of interest (VOI) in the distal metaphysis of each tibia, we show that the degree of anisotropy (DA) of trabecular struts changes with age. Intra-individual variation in DA across these VOIs is generally high at young ages, likely reflecting variation in loading due to kinematic instability. With increasing age, mean DA converges on higher values and becomes less variable across the distal tibia. We believe the ontogeny of distal tibia trabecular architecture reflects the development of locomotor stability in bipeds. We suggest this novel bony marker of development may be used to assess the relationship between locomotor development and other life history milestones in fossil hominins.

Muscle force production during bent-knee, bent-hip walking in humans.

Researchers have long debated the locomotor posture used by the earliest bipeds. While many agree that by 3-4 Ma (millions of years ago), hominins walked with an extended-limb human style of bipedalism, researchers are still divided over whether the earliest bipeds walked like modern humans, or walked with a more bent-knee, bent-hip (BKBH) ape-like form of locomotion. Since more flexed postures are associated with higher energy costs, reconstructing early bipedal mechanics has implications for the selection pressures that led to upright walking. The purpose of this study is to determine how modern human anatomy functions in BKBH walking to clarify the links between morphology and energy costs in different mechanical regimes. Using inverse dynamics, we calculated muscle force production at the major limb joints in humans walking in two modes, both with extended limbs and BKBH. We found that in BKBH walking, humans must produce large muscle forces at the knee to support body weight, leading to higher estimated energy costs. However, muscle forces at the hip remained similar in BKBH and extended limb walking, suggesting that anatomical adaptations for hip extension in humans do not necessarily diminish the effective mechanical advantage at the hip in more flexed postures. We conclude that the key adaptations for economical walking, regardless of joint posture, seem to center on maintaining low muscle forces at the hip, primarily by keeping low external moments at the hip. We explore the implications of these results for interpreting locomotor energetics in early hominins, including australopithecines and Ardipithecus ramidus.

Exercise-induced endocannabinoid signaling is modulated by intensity.

Endocannabinoids (eCB) are endogenous ligands for cannabinoid receptors that are densely expressed in brain networks responsible for reward. Recent work shows that exercise activates the eCB system in humans and other mammals, suggesting eCBs are partly responsible for the reported improvements in mood and affect following aerobic exercise in humans. However, exercise-induced psychological changes reported by runners are known to be dependent on exercise intensity, suggesting that any underlying molecular mechanism should also change with varying levels of exercise intensity. Here, we examine circulating levels of eCBs following aerobic exercise (treadmill running) in recreationally fit human runners at four different intensities. We show that eCB signaling is indeed intensity dependent, with significant changes in circulating eCBs observed following moderate intensities only (very high and very low intensity exercises do not significantly alter circulating eCB levels). Our results are consistent with intensity-dependent psychological state changes with exercise and therefore support the hypothesis that eCB activity is related to neurobiological effects of exercise. Thus, future studies examining the role of exercise-induced eCB signaling on neurobiology or physiology must take exercise intensity into account.

Wired to run: exercise-induced endocannabinoid signaling in humans and cursorial mammals with implications for the 'runner's high'.

Humans report a wide range of neurobiological rewards following moderate and intense aerobic activity, popularly referred to as the 'runner's high', which may function to encourage habitual aerobic exercise. Endocannabinoids (eCBs) are endogenous neurotransmitters that appear to play a major role in generating these rewards by activating cannabinoid receptors in brain reward regions during and after exercise. Other species also regularly engage in endurance exercise (cursorial mammals), and as humans share many morphological traits with these taxa, it is possible that exercise-induced eCB signaling motivates habitual high-intensity locomotor behaviors in cursorial mammals. If true, then neurobiological rewards may explain variation in habitual locomotor activity and performance across mammals. We measured circulating eCBs in humans, dogs (a cursorial mammal) and ferrets (a non-cursorial mammal) before and after treadmill exercise to test the hypothesis that neurobiological rewards are linked to high-intensity exercise in cursorial mammals. We show that humans and dogs share significantly increased exercise-induced eCB signaling following high-intensity endurance running. eCB signaling does not significantly increase following low-intensity walking in these taxa, and eCB signaling does not significantly increase in the non-cursorial ferrets following exercise at any intensity. This study provides the first evidence that inter-specific variation in neurotransmitter signaling may explain differences in locomotor behavior among mammals. Thus, a neurobiological reward for endurance exercise may explain why humans and other cursorial mammals habitually engage in aerobic exercise despite the higher associated energy costs and injury risks, and why non-cursorial mammals avoid such locomotor behaviors.

Laetoli footprints preserve earliest direct evidence of human-like bipedal biomechanics.

BACKGROUND: Debates over the evolution of hominin bipedalism, a defining human characteristic, revolve around whether early bipeds walked more like humans, with energetically efficient extended hind limbs, or more like apes with flexed hind limbs. The 3.6 million year old hominin footprints at Laetoli, Tanzania represent the earliest direct evidence of hominin bipedalism. Determining the kinematics of Laetoli hominins will allow us to understand whether selection acted to decrease energy costs of bipedalism by 3.6 Ma. METHODOLOGY/PRINCIPAL FINDINGS: Using an experimental design, we show that the Laetoli hominins walked with weight transfer most similar to the economical extended limb bipedalism of humans. Humans walked through a sand trackway using both extended limb bipedalism, and more flexed limb bipedalism. Footprint morphology from extended limb trials matches weight distribution patterns found in the Laetoli footprints. CONCLUSIONS: These results provide us with the earliest direct evidence of kinematically human-like bipedalism currently known, and show that extended limb bipedalism evolved long before the appearance of the genus Homo. Since extended-limb bipedalism is more energetically economical than ape-like bipedalism, energy expenditure was likely an important selection pressure on hominin bipeds by 3.6 Ma.