Severe PTSD is marked by reduced oxytocin and elevated vasopressin.

Neuroendocrine analyses of posttraumatic stress disorder (PTSD) have generally focused on hypothalamic-pituitary-adrenal (HPA) axis alterations. In the present analyses, we examine two additional neuroendocrine factors that have been previously implicated in biological stress responses: oxytocin (OT) and arginine vasopressin (AVP). Here we examined basal neuropeptide status in military veterans clinically diagnosed with PTSD (n = 29) and in two non-traumatized comparison groups with previous stress exposure (n = 11 SWAT trainees and n = 21 ultramarathon runners). PTSD patients showed low levels of plasma OT and high levels of AVP. The ratio of AVP/OT robustly related to PTSD status, and emerged as a statistically plausible mediator of relationships between the number of personal traumatic experiences and subsequent PTSD symptom burden. Over the course of behavioral therapy for PTSD, measures of OT showed a significant but modest normalization. Plasma cortisol levels were not statistically different among the three groups. This study suggests that AVP/OT ratios may represent a neuroendocrine predictor of severe PTSD, as well as a potential treatment response biomarker.

Mechanistic insight into the role of AUXIN RESISTANCE4 in trafficking of AUXIN1 and LIKE AUX1-2.

AUXIN RESISTANCE4 (AXR4) regulates the trafficking of auxin influx carrier AUXIN1 (AUX1), a plasma-membrane protein that predominantly localizes to the endoplasmic reticulum (ER) in the absence of AXR4. In Arabidopsis (Arabidopsis thaliana), AUX1 is a member of a small multigene family comprising 4 highly conserved genes-AUX1, LIKE-AUX1 (LAX1), LAX2, and LAX3. We report here that LAX2 also requires AXR4 for correct localization to the plasma membrane. AXR4 is a plant-specific protein and contains a weakly conserved α/ß hydrolase fold domain that is found in several classes of lipid hydrolases and transferases. We have previously proposed that AXR4 may either act as (i) a post-translational modifying enzyme through its α/ß hydrolase fold domain or (ii) an ER accessory protein, which is a special class of ER protein that regulates targeting of their cognate partner proteins. Here, we show that AXR4 is unlikely to act as a post-translational modifying enzyme as mutations in several highly conserved amino acids in the α/ß hydrolase fold domain can be tolerated and active site residues are missing. We also show that AUX1 and AXR4 physically interact with each other and that AXR4 reduces aggregation of AUX1 in a dose-dependent fashion. Our results suggest that AXR4 acts as an ER accessory protein. A better understanding of AXR4-mediated trafficking of auxin transporters in crop plants will be crucial for improving root traits (designer roots) for better acquisition of water and nutrients for sustainable and resilient agriculture.

Axial muscle activation provides stabilization against perturbations while running.

Incidence of traumatic brain injury is an important hazard in sports and recreation. Unexpected (blind-sided) impacts with other players, obstacles, and the ground can be particularly dangerous. We believe this is partially due to the lack of muscular activation which would have otherwise provided protective bracing. In this study participants were asked to run on the treadmill while undergoing perturbations applied at the waist which pulled participants in the fore-aft and lateral directions. To determine the effect of unexpected impacts, participants were given a directional audio-visual warning 0.5 s prior to the perturbation in half of the trials and were unwarned in the other half of the trials. Perturbations were given during the start of the stance phase and during the start of the flight phase to examine two distinct points within the locomotor cycle. Muscle activity was monitored in axial muscles before, during, and after the perturbations were given. We hypothesized that the presence of a warning would allow for voluntary axial muscle activity prior to and during perturbations that would provide bracing of the body, and decreased displacement and acceleration of the head compared to unwarned perturbations. Our results indicate that when a warning is given prior to perturbation, the body was displaced significantly less, and the linear acceleration of the head was also significantly lessened in response to some perturbations. The perturbations given in this study caused significant increases in axial muscle activity compared to activity present during control running. We found evidence that cervical and abdominal muscles increased activity in response to the warning and that typically the warned trials displayed a lower reflexive muscle activity response. Additionally, we found a stronger effect of the warnings on muscle activity within the perturbations given during flight phase than those given at stance phase. Results from this study support the hypothesis that knowledge regarding an impending perturbation is used by the neuromuscular system to activate relevant core musculature and provide bracing to the athlete.

PIEZO1 and PECAM1 interact at cell-cell junctions and partner in endothelial force sensing.

Two prominent concepts for the sensing of shear stress by endothelium are the PIEZO1 channel as a mediator of mechanically activated calcium ion entry and the PECAM1 cell adhesion molecule as the apex of a triad with CDH5 and VGFR2. Here, we investigated if there is a relationship. By inserting a non-disruptive tag in native PIEZO1 of mice, we reveal in situ overlap of PIEZO1 with PECAM1. Through reconstitution and high resolution microscopy studies we show that PECAM1 interacts with PIEZO1 and directs it to cell-cell junctions. PECAM1 extracellular N-terminus is critical in this, but a C-terminal intracellular domain linked to shear stress also contributes. CDH5 similarly drives PIEZO1 to junctions but unlike PECAM1 its interaction with PIEZO1 is dynamic, increasing with shear stress. PIEZO1 does not interact with VGFR2. PIEZO1 is required in Ca2+-dependent formation of adherens junctions and associated cytoskeleton, consistent with it conferring force-dependent Ca2+ entry for junctional remodelling. The data suggest a pool of PIEZO1 at cell junctions, the coming together of PIEZO1 and PECAM1 mechanisms and intimate cooperation of PIEZO1 and adhesion molecules in tailoring junctional structure to mechanical requirement.

The Human Neck is Part of the Musculoskeletal Core: Cervical Muscles Help Stabilize the Pelvis During Running and Jumping.

During locomotion, cervical muscles must be active to stabilize the head as the body accelerates and decelerates. We hypothesized that cervical muscles are also part of the linked chain of axial muscles that provide core stabilization against torques applied to the hip joint by the extrinsic muscles of the legs. To test whether specific cervical muscles play a role in postural stabilization of the head and/or core stabilization of the pelvic girdle, we used surface electromyography to measure changes in muscle activity in response to force manipulations during constant speed running and maximum effort counter-movement jumps. We found that doubling the mass of the head during both running and maximum effort jumping had little or no effect on (1) acceleration of the body and (2) cervical muscle activity. Application of horizontal forward and rearward directed forces at the pelvis during running tripled mean fore and aft accelerations, thereby increasing both the pitching moments on the head and flexion and extension torques applied to the hip. These manipulations primarily resulted in increases in cervical muscle activity that is appropriate for core stabilization of the pelvis. Additionally, when subjects jumped maximally with an applied downward directed force that reduced acceleration and therefore need for cervical muscles to stabilize the head, cervical muscle activity did not decrease. These results suggest that during locomotion, rather than acting to stabilize the head against the effects of inertia, the superficial muscles of the neck monitored in this study help to stabilize the pelvis against torques imposed by the extrinsic muscles of the legs at the hip joint. We suggest that a division of labor may exist between deep cervical muscles that presumably provide postural stabilization of the head versus superficial cervical muscles that provide core stabilization against torques applied to the pelvic and pectoral girdles by the extrinsic appendicular muscles.

Durante la locomoción, los músculos cervicales deben estar activos para estabilizar la cabeza a medida que el cuerpo acelera y desacelera. Presumimos que los músculos cervicales también son parte de la cadena unida de músculos axiales que brindan estabilización central contra las torsiones aplicadas a la articulación de la cadera por los músculos extrínsecos de las piernas. Para evaluar si los músculos cervicales específicos desempeñan un papel en la estabilización postural de la cabeza y/o la estabilización central de la cintura pélvica, utilizamos electromiografía de superficie para medir los cambios en la actividad muscular en respuesta a las manipulaciones de fuerza durante la carrera a velocidad constante y los saltos con contramovimiento de esfuerzo máximo. Descubrimos que duplicar la masa de la cabeza durante la carrera y el salto de máximo esfuerzo tuvo poco o ningún efecto sobre (1) la aceleración del cuerpo y (2) la actividad de los músculos cervicales. La aplicación de fuerzas horizontales dirigidas hacia adelante y hacia atrás en la pelvis durante la carrera triplicó las aceleraciones medias hacia adelante y hacia atrás, aumentando así tanto los momentos de cabeceo en la cabeza como los pares de flexión y extensión aplicados a la cadera. Estas manipulaciones dieron como resultado principalmente aumentos en la actividad de los músculos cervicales que son apropiados para la estabilización central de la pelvis. Además, cuando los sujetos saltaban al máximo aplicando una fuerza dirigida hacia abajo que reducía la aceleración y, por lo tanto, la necesidad de los músculos cervicales para estabilizar la cabeza, la actividad de los músculos cervicales no disminuía. Sugerimos que puede existir una división del trabajo entre los músculos cervicales profundos que presumiblemente brindan estabilización postural de la cabeza versus los músculos cervicales superficiales que brindan estabilización central contra los torques aplicados a las cinturas pélvica y pectoral por los músculos apendiculares extrínsecos.

Pendant la locomotion, les muscles cervicaux doivent être actifs pour stabiliser la tête lorsque le corps accélère et décélère. Nous avons émis l"hypothèse que les muscles cervicaux font également partie de la chaîne liée des muscles axiaux qui assurent la stabilisation du noyau contre les couples appliqués à l"articulation de la hanche par les muscles extrinsèques des jambes. Pour tester si des muscles cervicaux spécifiques jouent un rôle dans la stabilisation posturale de la tête et/ou la stabilisation centrale de la ceinture pelvienne, nous avons utilisé l"électromyographie de surface pour mesurer les changements dans l"activité musculaire en réponse aux manipulations de force pendant la course à vitesse constante et les sauts de contre-mouvement à effort maximal. Nous avons constaté que doubler la masse de la tête pendant la course et le saut à effort maximal avait peu ou pas d"effet sur (1) l"accélération du corps et (2) l"activité des muscles cervicaux. L"application de forces horizontales dirigées vers l"avant et vers l"arrière au niveau du bassin pendant la course a triplé les accélérations moyennes vers l"avant et vers l"arrière, augmentant ainsi à la fois les moments de tangage sur la tête et les couples de flexion et d"extension appliqués à la hanche. Ces manipulations ont principalement entraîné une augmentation de l"activité des muscles cervicaux, ce qui est approprié pour la stabilisation centrale du bassin. De plus, lorsque les sujets sautaient au maximum avec une force dirigée vers le bas qui réduisait l"accélération et donc le besoin de muscles cervicaux pour stabiliser la tête, l"activité des muscles cervicaux ne diminuait pas. Ces résultats suggèrent que lors de la locomotion, plutôt que d"agir pour stabiliser la tête contre les effets de l"inertie, les muscles superficiels du cou suivis dans cette étude aident à stabiliser le bassin contre les couples imposés par les muscles extrinsèques des jambes au niveau de l"articulation de la hanche. Nous suggérons qu"une division du travail peut exister entre les muscles cervicaux profonds qui assurent vraisemblablement la stabilisation posturale de la tête et les muscles cervicaux superficiels qui assurent la stabilisation centrale contre les couples appliqués aux ceintures pelvienne et pectorale par les muscles appendiculaires extrinsèques.

Climbing parrots achieve pitch stability using forces and free moments produced by axial-appendicular couples.

During vertical climbing, the gravitational moment tends to pitch the animal's head away from the climbing surface and this may be countered by (1) applying a correcting torque at a discrete contact point, or (2) applying opposing horizontal forces at separate contact points to produce a free moment. We tested these potential strategies in small parrots with an experimental climbing apparatus imitating the fine branches and vines of their natural habitat. The birds climbed on a vertical ladder with four instrumented rungs that measured three-dimensional force and torque, representing the first measurements of multiple contacts from a climbing bird. The parrots ascend primarily by pulling themselves upward using the beak and feet. They resist the gravitational pitching moment with a free moment produced by horizontal force couples between the beak and feet during the first third of the stride and the tail and feet during the last third of the stride. The reaction torque from individual rungs did not counter, but exacerbated the gravitational pitching moment, which was countered entirely by the free moment. Possible climbing limitations were explored using two different rung radii, each with low and high friction surfaces. Rung torque was limited in the large-radius, low-friction condition; however, rung condition did not significantly influence the free moments produced. These findings have implications for our understanding of avian locomotor modules (i.e. coordinated actions of the head-neck, hindlimbs and tail), the use of force couples in vertical locomotion, and the evolution of associated structures.

Great power comes at a high (locomotor) cost: the role of muscle fascicle length in the power versus economy performance trade-off.

Muscle design constraints preclude simultaneous specialization of the vertebrate locomotor system for explosive and economical force generation. The resulting performance trade-off between power and economy has been attributed primarily to individual differences in muscle fiber type composition. While certainly crucial for performance specialization, fiber type likely interacts with muscle architectural parameters, such as fascicle length, to produce this trade-off. Longer fascicles composed of more serial sarcomeres can achieve faster shortening velocities, allowing for greater power production. Long fascicles likely reduce economy, however, because more energy-consuming contractile units are activated for a given force production. We hypothesized that longer fascicles are associated with both increased power production and locomotor cost. In 11 power-trained and 13 endurance-trained recreational athletes, we measured (1) muscle fascicle length via ultrasound in the gastrocnemius lateralis, gastrocnemius medialis and vastus lateralis, (2) maximal power during cycling and countermovement jumps, and (3) running cost of transport. We estimated muscle fiber type non-invasively based on the pedaling rate at which maximal cycling power occurred. As predicted, longer gastrocnemius muscle fascicles were correlated with greater lower-body power production and cost of transport. Multiple regression analyses revealed that variability in maximal power was explained by fiber type (46% for cycling, 24% for jumping) and average fascicle length (20% for cycling, 13% for jumping), while average fascicle length accounted for 15% of the variation in cost of transport. These results suggest that, at least for certain muscles, fascicle length plays an important role in the power versus economy performance trade-off.

Musculoskeletal mass and shape are correlated with competitive ability in male house mice (Mus musculus).

Intense physical competition between males for mating opportunities is widespread among mammals. In such agonistic encounters, males with combinations of morphological, physiological and behavioral characters that allow them to dominate an opponent have greater fitness. However, the specific physical traits associated with competitive ability are poorly understood. Larger body size is often correlated with fitness in mammals. Interestingly, fitness is maximized at intermediate body masses in male house mice (Mus musculus), a species with a polygynous mating system in which males compete physically for access to reproductive resources. Here, we used competition trials in semi-natural, mixed-sex population enclosures to directly measure competitive ability in male house mice based on control of a preferred nesting site. We tested the hypothesis that the musculoskeletal systems of male mice demonstrating high competitive ability are more specialized for competition by comparing the masses of 10 major muscle groups and eight bones as well as a set of 12 skeletal shape indices associated with anatomical specialization for fighting performance in a set of nine winners and 20 losers. Winning males possessed several traits hypothesized to enhance performance in male-male contests: relatively greater mass in several muscle groups and bones of the forelimb and hindlimb and larger scapular surface area. Unexpectedly, no measurements of the head and neck differed significantly between winners and losers. These results identify musculoskeletal traits associated with competitive ability in male house mice and suggest that our current understanding of mammalian fighting performance is incomplete and more nuanced than previously considered.

Sexual dimorphism in human arm power and force: implications for sexual selection on fighting ability.

Sexual dimorphism often arises from selection on specific musculoskeletal traits that improve male fighting performance. In humans, one common form of fighting includes using the fists as weapons. Here, we tested the hypothesis that selection on male fighting performance has led to the evolution of sexual dimorphism in the musculoskeletal system that powers striking with a fist. We compared male and female arm cranking power output, using it as a proxy for the power production component of striking with a fist. Using backward arm cranking as an unselected control, our results indicate the presence of pronounced male-biased sexual dimorphism in muscle performance for protracting the arm to propel the fist forward. We also compared overhead pulling force between males and females, to test the alternative hypothesis that sexual dimorphism in the upper body of humans is a result of selection on male overhead throwing ability. We found weaker support for this hypothesis, with less pronounced sexual dimorphism in overhead arm pulling force. The results of this study add to a set of recently identified characters indicating that sexual selection on male aggressive performance has played a role in the evolution of the human musculoskeletal system and the evolution of sexual dimorphism in hominins.

Mutagenesis separates ATPase and thioesterase activities of the peroxisomal ABC transporter, Comatose.

The peroxisomal ABC transporter, Comatose (CTS), a full length transporter from Arabidopsis has intrinsic acyl-CoA thioesterase (ACOT) activity, important for physiological function. We used molecular modelling, mutagenesis and biochemical analysis to identify amino acid residues important for ACOT activity. D863, Q864 and T867 lie within transmembrane helix 9. These residues are orientated such that they might plausibly contribute to a catalytic triad similar to type II Hotdog fold thioesterases. When expressed in Saccharomyces cerevisiae, mutation of these residues to alanine resulted in defective of ß-oxidation. All CTS mutants were expressed and targeted to peroxisomes and retained substrate-stimulated ATPase activity. When expressed in insect cell membranes, Q864A and S810N had similar ATPase activity to wild type but greatly reduced ACOT activity, whereas the Walker A mutant K487A had greatly reduced ATPase and no ATP-dependent ACOT activity. In wild type CTS, ATPase but not ACOT was stimulated by non-cleavable C14 ether-CoA. ACOT activity was stimulated by ATP but not by non-hydrolysable AMPPNP. Thus, ACOT activity depends on functional ATPase activity but not vice versa, and these two activities can be separated by mutagenesis. Whether D863, Q864 and T867 have a catalytic role or play a more indirect role in NBD-TMD communication is discussed.

An outside-the-box activity to demonstrate how humans and animals turn.

Developing hands-on activities that engage and excite K-12 students is critical for stimulating interest in science-based careers. We created an activity for high school students that required them to integrate biology and physics concepts to experience how humans and animals maneuver through their environments (i.e., turning). Understanding how turning works is important because it accounts for up to 50% of daily walking steps and is needed for survival when animals elude predators and capture prey. For this activity, student groups used 2 × 4 lumber, wood screws, and a power drill to build an apparatus that, when connected to the body, altered rotational inertia (object's resistance to change in angular motion, I = mass × radius2). Students navigated through a slalom course with the apparatus (increased radius and rotational inertia) and without the apparatus (mass-matched control). Times to complete the course were compared between trials to determine the influence of rotational inertia on turning performance. Students compiled their data, graphed their results, and found that increased rotational inertia decreased turning performance. Results were connected to sports, rehabilitation, and dinosaur evolution. This activity was implemented during local, regional, national, and international outreach events and adapted for use in undergraduate courses as well (total impact, 250 students). At the end of the activity, students were able to 1) describe whether their results supported their hypothesis; 2) explain how radius influences rotational inertia and turning performance; and 3) apply results to real-world examples. Students and teachers appreciated this "outside-the-box" activity with an engineering twist and found it entertaining.

Sexual dimorphism in postcranial skeletal shape suggests male-biased specialization for physical competition in anthropoid primates.

Sexual dimorphism often arises as a response to selection on traits that improve a male's ability to physically compete for access to mates. In primates, sexual dimorphism in body mass and canine size is more common in species with intense male-male competition. However, in addition to these traits, other musculoskeletal adaptations may improve male fighting performance. Postcranial traits that increase strength, agility, and maneuverability may also be under selection. To test the hypothesis that males, as compared to females, are more specialized for physical competition in their postcranial anatomy, we compared sex-specific skeletal shape using a set of functional indices predicted to improve fighting performance. Across species, we found significant sexual dimorphism in a subset of these indices, indicating the presence of skeletal shape sexual dimorphism in our sample of anthropoid primates. Mean skeletal shape sexual dimorphism was positively correlated with sexual dimorphism in body size, an indicator of the intensity of male-male competition, even when controlling for both body mass and phylogenetic relatedness. These results suggest that selection on male fighting ability has played a role in the evolution of postcranial sexual dimorphism in primates.

Changes in collegiate ice hockey player anthropometrics and aerobic fitness over 3 decades.

Over the past several decades, an increased emphasis on fitness training has emerged among collegiate ice hockey teams, with the objective of improving on-ice performance. However, it is unknown if this increase in training has translated over time into changes in the anthropometric and fitness profiles of collegiate ice hockey players. The purposes of this study were to describe anthropometric (height, weight, body mass index (BMI), percent body fat (%fat)) and aerobic fitness (peak oxygen consumption) characteristics of collegiate ice hockey players over a period of 36 years and to evaluate whether these characteristics differ among player positions. Anthropometric and physiologic data were obtained through preseason fitness testing of players (N = 279) from a National Collegiate Athletic Association Division I men's ice hockey team from the years 1980 through 2015. Changes over time in the anthropometric and physiologic variables were evaluated via regression analysis using linear and polynomial models, and differences among player positions were compared via ANOVA (p < 0.05). Regression analysis revealed that a cubic model best predicted changes in mean height (R2 = 0.65), weight (R2 = 0.77), and BMI (R2 = 0.57), whereas a quadratic model best fit change in %fat by year (R2 = 0.30). Little change was observed over time in the anthropometric characteristics. Defensemen were significantly taller than forwards (184.7 ± 12.1 vs. 181.3 ± 5.9 cm) (p = 0.007), and forwards had a higher relative peak oxygen consumption compared with defensemen (58.7 ± 4.7 vs. 57.2 ± 4.4 mL·kg-1·min-1) (p = 0.032). No significant differences were observed in %fat or weight by position. Although average player heights and weights fluctuated over time, increased emphasis on fitness training did not affect the athletes' relative aerobic fitness. Differences in height and aerobic fitness levels were observed among player positions.

A disparity between locomotor economy and territory-holding ability in male house mice.

Both economical locomotion and physical fighting are important performance traits to many species because of their direct influence on components of Darwinian fitness. Locomotion represents a substantial portion of the total daily energy budget of many animals. Fighting performance often determines individual reproductive fitness through the means of resource control, social dominance and access to mates. However, phenotypic traits that improve either locomotor economy or fighting ability may diminish performance in the other. Here, we tested for a predicted disparity between locomotor economy and competitive ability in wild-derived house mice (Mus musculus). We used 8 week social competition trials in semi-natural enclosures to directly measure male competitive ability through territorial control and female occupancy within territories. We also measured oxygen consumption during locomotion for each mouse using running trials in an enclosed treadmill and open-flow respirometry. Our results show that territory-holding males have higher absolute and mass-specific oxygen consumption when running (i.e. reduced locomotor economy) compared with males that do not control territories. This relationship was present both before and after 8 week competition trials in semi-natural enclosures. This disparity between physical competitive ability and economical locomotion may impose viability costs on males in species for which competition over mates is common and may constrain the evolution of behavioral and phenotypic diversity, particularly in natural settings with environmental and resource variability.

The effect of foot posture on capacity to apply free moments to the ground: implications for fighting performance in great apes.

In contrast to most other primates, great apes have feet in which the heel supports body weight during standing, walking and running. One possible advantage of this plantigrade foot posture is that it may enhance fighting performance by increasing the ability to apply free moments (i.e. force couples) to the ground. We tested this possibility by measuring performance of human subjects when performing from plantigrade and digitigrade (standing on the ball of the foot and toes) postures. We found that plantigrade posture substantially increased the capacity to apply free moments to the ground and to perform a variety of behaviors that are likely to be important to fighting performance in great apes. As predicted, performance in maximal effort lateral striking and pushing was strongly correlated with free moment magnitude. All else being equal, these results suggest species that can adopt plantigrade posture will be able to apply larger free moments to the ground than species restricted to digitigrade or unguligrade foot posture. Additionally, these results are consistent with the suggestion that selection for physical competition may have been one of the factors that led to the evolution of the derived plantigrade foot posture of great apes.

How to move an amphipathic molecule across a lipid bilayer: different mechanisms for different ABC transporters?

Import of ß-oxidation substrates into peroxisomes is mediated by ATP binding cassette (ABC) transporters belonging to subfamily D. In order to enter the ß-oxidation pathway, fatty acids are activated by conversion to fatty acyl-CoA esters, a reaction which is catalysed by acyl-CoA synthetases (ACSs). Here, we present evidence for an unusual transport mechanism, in which fatty acyl-CoA substrates are accepted by ABC subclass D protein (ABCD) transporters, cleaved by the transporters during transit across the lipid bilayer to release CoA, and ultimately re-esterified in the peroxisome lumen by ACSs which interact with the transporter. We propose that this solves the biophysical problem of moving an amphipathic molecule across the peroxisomal membrane, since the intrinsic thioesterase activity of the transporter permits separate membrane translocation pathways for the hydrophobic fatty acid moiety and the polar CoA moiety. The cleavage/re-esterification mechanism also has the potential to control entry of disparate substrates into the ß-oxidation pathway when coupled with distinct peroxisomal ACSs. A different solution to the movement of amphipathic molecules across a lipid bilayer is deployed by the bacterial lipid-linked oligosaccharide (LLO) flippase, PglK, in which the hydrophilic head group and the hydrophobic polyprenyl tail of the substrate are proposed to have distinct translocation pathways but are not chemically separated during transport. We discuss a speculative alternating access model for ABCD proteins based on the mammalian ABC transporter associated with antigen processing (TAP) and compare it to the novel mechanism suggested by the recent PglK crystal structures and biochemical data.

Architecture of the sperm whale forehead facilitates ramming combat.

Herman Melville's novel Moby Dick was inspired by historical instances in which large sperm whales (Physeter macrocephalus L.) sank 19th century whaling ships by ramming them with their foreheads. The immense forehead of sperm whales is possibly the largest, and one of the strangest, anatomical structures in the animal kingdom. It contains two large oil-filled compartments, known as the "spermaceti organ" and "junk," that constitute up to one-quarter of body mass and extend one-third of the total length of the whale. Recognized as playing an important role in echolocation, previous studies have also attributed the complex structural configuration of the spermaceti organ and junk to acoustic sexual selection, acoustic prey debilitation, buoyancy control, and aggressive ramming. Of these additional suggested functions, ramming remains the most controversial, and the potential mechanical roles of the structural components of the spermaceti organ and junk in ramming remain untested. Here we explore the aggressive ramming hypothesis using a novel combination of structural engineering principles and probabilistic simulation to determine if the unique structure of the junk significantly reduces stress in the skull during quasi-static impact. Our analyses indicate that the connective tissue partitions in the junk reduce von Mises stresses across the skull and that the load-redistribution functionality of the former is insensitive to moderate variation in tissue material parameters, the thickness of the partitions, and variations in the location and angle of the applied load. Absence of the connective tissue partitions increases skull stresses, particularly in the rostral aspect of the upper jaw, further hinting of the important role the architecture of the junk may play in ramming events. Our study also found that impact loads on the spermaceti organ generate lower skull stresses than an impact on the junk. Nevertheless, whilst an impact on the spermaceti organ would reduce skull stresses, it would also cause high compressive stresses on the anterior aspect of the organ and the connective tissue case, possibly making these structures more prone to failure. This outcome, coupled with the facts that the spermaceti organ houses sensitive and essential sonar producing structures and the rostral portion of junk, rather than the spermaceti organ, is frequently a site of significant scarring in mature males suggest that whales avoid impact with the spermaceti organ. Although the unique structure of the junk certainly serves multiple functions, our results are consistent with the hypothesis that the structure also evolved to function as a massive battering ram during male-male competition.

Sexual selection on skeletal shape in Carnivora.

Lifetime reproductive success of males is often dependent upon the ability to physically compete for mates. However, species variation in social structure leads to differences in the relative importance of intraspecific aggression. Here, we present a large comparative dataset on sexual dimorphism in skeletal shape in Carnivora to test the hypotheses that carnivorans exhibit sexual dimorphism in skeletal anatomy that is reflective of greater specialization for physical aggression in males relative to females and that this dimorphism is associated with the intensity of sexual selection. We tested these hypotheses using a set of functional indices predicted to improve aggressive performance. Our results indicate that skeletal shape dimorphism is widespread within our sample. Functional traits thought to enhance aggressive performance are more pronounced in males. Phylogenetic model selection suggests that the evolution of this dimorphism is driven by sexual selection, with the best-fitting model indicating greater dimorphism in polygynous versus nonpolygynous species. Skeletal shape dimorphism is correlated with body size dimorphism, a common indicator of the intensity of male-male competition, but not with mean body size. These results represent the first evidence of sexual dimorphism in the primary locomotor system of a large sample of mammals.

Manipulated Changes in Limb Mass and Rotational Inertia in Trotting Dogs (Canis lupus familiaris) and Their Effect on Limb Kinematics.

While the mass distribution of limbs is known to influence the metabolic energy consumed during locomotion, it remains unknown how the mass distribution of limbs may influence overall limb kinematics and whether the influence of limb mass distribution on limb kinematics differs between fore- and hindlimbs. To examine limb mass distribution's influence upon fore- and hindlimb kinematics, temporal stride parameters and swing phase joint kinematics were recorded from four dogs trotting on a treadmill with 0.5% and 1.0% body mass added to each limb, forelimbs alone, and hindlimbs alone, as well as with no added mass. Under all loading conditions, stride period did not differ between fore- and hindlimbs; however, forelimbs exhibited greater duty factors and stance durations, whereas hindlimbs exhibited greater swing durations, which may be related to the hindlimb's greater mass. Changes in forelimb joint and hip range of motion (RoM), flexion, and extension were subject to a high amount of kinematic plasticity among dogs. In contrast, for the knee and ankle, distally loading all four limbs or hindlimbs alone substantially increased joint RoM and flexion. Increased flexion of the knee and ankle has the potential to reduce the hindlimb's rotational inertia during swing phase. The differing response of fore- and hindlimbs with regard to joint kinematics is likely due to differences in their mass and mass distribution and differences in the physiological traits of fore- and hindlimb protractors and joint flexors.

Muscle activation during maximal effort tasks: evidence of the selective forces that shaped the musculoskeletal system of humans.

The selective forces that played a role in the evolution of the musculoskeletal system of the genus Homo have long been debated and remain poorly understood. In this investigation, we introduce a new approach for testing alternative hypotheses. Our analysis is based on the premise that natural selection can be expected to have resulted in muscles that are large enough to achieve necessary levels of maximum performance in essential behaviors, but not larger. We used surface electromyography in male subjects to identify maximum activation levels in 13 muscles of the back and leg during eight behaviors that have been suggested to have been important to foraging, hunting and fighting performance in early humans. We asked two questions: (1) what behaviors produce maximum activation in each of the investigated muscles and (2) are there specific behaviors that elicit maximum recruitment from all or most of the muscles? We found that in eight of the 13 muscles, the highest activity occurred during maximal effort vertical jumping (i.e. whole-body acceleration). Punching produced the highest median activity in the other five muscles. Together, jumping and punching accounted for 73% of the incidences of maximum activity among all of the muscles and from all of the subjects. Thus, the size of the muscles of the back and leg appear to be more related to the demands of explosive behaviors rather than those of high speed sprinting or sustained endurance running. These results are consistent with the hypothesis that selection on aggressive behavior played an important role in the evolution of the genus Homo.