The mechanics of head-supported load carriage by Nepalese porters.

In the Everest valley of Nepal, because of the rugged mountain terrain, roads are nothing more than dirt paths and all material must be conveyed on foot. The Nepalese porters routinely carry head-supported loads, which often exceed their body mass, over long distances up and down the steep mountain footpaths. In Africa, women transport their loads economically thanks to an energy-saving gait adaptation. We hypothesized that the Nepalese porters may have developed a corresponding mechanism. To investigate this proposition, we measured the mechanical work done during level walking in Nepalese porters while carrying different loads at several speeds. Our results show that the Nepalese porters do not use an equivalent mechanism as the African women to reduce work. In contrast, the Nepalese porters develop an equal amount of total mechanical work as Western control subjects while carrying loads of 0 to 120% of their body mass at all speeds measured (0.5-1.7 m s-1), making even more impressive their ability to carry loads without any apparent mechanically determined tricks. Nevertheless, our results show that the Nepalese porters have a higher efficiency, at least at slow speeds and high loads.

Developing 3D SEM in a broad biological context.

When electron microscopy (EM) was introduced in the 1930s it gave scientists their first look into the nanoworld of cells. Over the last 80 years EM has vastly increased our understanding of the complex cellular structures that underlie the diverse functions that cells need to maintain life. One drawback that has been difficult to overcome was the inherent lack of volume information, mainly due to the limit on the thickness of sections that could be viewed in a transmission electron microscope (TEM). For many years scientists struggled to achieve three-dimensional (3D) EM using serial section reconstructions, TEM tomography, and scanning EM (SEM) techniques such as freeze-fracture. Although each technique yielded some special information, they required a significant amount of time and specialist expertise to obtain even a very small 3D EM dataset. Almost 20 years ago scientists began to exploit SEMs to image blocks of embedded tissues and perform serial sectioning of these tissues inside the SEM chamber. Using first focused ion beams (FIB) and subsequently robotic ultramicrotomes (serial block-face, SBF-SEM) microscopists were able to collect large volumes of 3D EM information at resolutions that could address many important biological questions, and do so in an efficient manner. We present here some examples of 3D EM taken from the many diverse specimens that have been imaged in our core facility. We propose that the next major step forward will be to efficiently correlate functional information obtained using light microscopy (LM) with 3D EM datasets to more completely investigate the important links between cell structures and their functions.

The mechanics of jumping over an obstacle during running: a comparison between athletes trained to hurdling and recreational runners.

PURPOSE: This study compares the mechanism of running in trained athletes (TA) experienced in hurdling and in recreational runners (RR), as they approach and jump over an obstacle. METHODS: The movements of the centre of mass of the body (COM), the external muscular work (W ext) and the leg-spring stiffness (k leg) were evaluated in athletes approaching an obstacle at 18 km h(-1), from the ground reaction forces (measured by force-platforms) and the orientation of the lower-limb segments (measured by camera). These results were compared to those obtained in RR. RESULTS: Two steps before the obstacle, k leg is reduced by 10-20 %; so, the COM is lowered and accelerated forward. During the step preceding the obstacle, k leg is increased by 40-60 %; so the COM is raised and accelerated upwards, whereas its forward velocity is reduced. This change in the running pattern is similar to the one observed in RR while leaping an obstacle. However, in TA, the change in stiffness is less pronounced. As a result, the orientation of the velocity vector at the beginning of the aerial phase over the obstacle is more horizontal than in RR, which involves a 10-20 % greater horizontal velocity and a 40-60 % smaller vertical excursion of the COM when crossing the obstacle; subsequently, W ext during contact before the obstacle is 10-20 % less. CONCLUSION: Athletes use the same mechanisms as non-specialists to cross an obstacle. However, athletes adapt the mechanism of jumping to reduce the loss in the velocity of progression when crossing an obstacle.

The mechanics of running while approaching and jumping over an obstacle.

When leaping an obstacle, the runner increases the vertical velocity of his/her centre of mass (COM) at takeoff to augment the amplitude and duration of the aerial phase over it. This study analyses the modification of the bouncing mechanism of running when approaching a barrier. The forces exerted by the feet on the ground are measured by a 13-m-long force platform during the four to nine running steps preceding the jump over a 0.45- to 0.85-m-high barrier, at an approaching speed between 9 and 21 km h(-1). The movements of the COM are evaluated by time-integration of the forces and the stiffness of the bouncing system by computer simulation. The running mechanism is modified during the two steps preceding the barrier. During the contact period, two steps before the barrier, the leg-spring stiffness decreases; consequently, the COM is lowered and accelerated forward. Then during the contact period preceding the obstacle, the leg-spring stiffness increases and the COM is raised and accelerated upwards, whereas its forward velocity is reduced. During this phase, the leg-spring acts like a pole, which stores elastic energy and changes the direction of the velocity vector to release this energy in a vertical direction. At high speeds, this storage-release mechanism of elastic energy is sufficient to provide the energy necessary to leap the obstacle. On the contrary, at low speeds, the amount of elastic energy stored and released in the leg-spring is not sufficient to jump over the obstacle and additional positive muscular work must be done.

Motor control of landing in an unsteady environment.

BACKGROUND: When landing from a jump or a drop, muscles contract before touchdown to anticipate imminent collision with the ground, soften ground contact and allow to return to a stable standing position without stepping or rebounding. RESEARCH QUESTION: This study assesses the effect of the unsteadiness of the environment on the motor control of landing. The 'unsteady environment' was induced by asking participants to perform drop landings inside an aircraft that underwent trajectories parallel to Earth's surface. The participants also performed the same task in a 'steady environment' in our laboratory. METHODS: Ground reaction forces, lower limb joints' movements and the activity of lower limb muscles were recorded. The stability of the landing was assessed by the vertical and anterior-posterior stability indexes, center of pressure measures and by the coefficient of variation of kinetic and kinematic parameters. RESULTS: On one hand, participants slowdown their joint movements and reduce the knee joint excursion during landing, probably to avoid excessive movements that may induce imbalance. On the other hand, the stability of the landing is reduced while the variability of the movement is increased, illustrating a less stable and less consistent landing. In addition, whatever the environment, landing parameters associated with increased stiffness (i.e., increased impact forces and decreased joint range of motion) are correlated with decreased landing stability. SIGNIFICANCE: Overall, landings in the'unsteady environment' appear to be more cautious but less stable and less finely tuned. Since the stability of the landing is not directly influenced by the steadiness of the environment, this more cautious behavior could be, at least in part, related to the fear/apprehension induced by sudden acceleration variations of the frame of the aircraft.

Identification of polymorphisms in the ovine Shadow of prion protein (SPRN) gene and assessment of their effect on promoter activity and susceptibility for classical scrapie.

Shadow of prion protein (SPRN) is an interesting candidate gene thought to be involved in prion pathogenesis. In humans, an association has already been discovered between mutations in SPRN and the incidence of variant and sporadic Creutzfeldt-Jakob disease. However, in sheep, the effect of mutations in SPRN is largely unknown. Therefore, we analysed the presence of mutations in the entire ovine SPRN gene, their association with scrapie susceptibility and their effect on SPRN promoter activity. In total, 26 mutations were found: seven in the promoter region, four in intron 1, seven in the coding sequence and eight in the 3' untranslated region. The mutations detected in the coding sequence and the promoter region were subsequently analysed in more detail. In the coding sequence, a polymorphism causing a deletion of two alanines was found to be associated with susceptibility for classical scrapie in sheep. Furthermore, a functional analysis of deletion constructs of the ovine SPRN promoter revealed that the region 464 to 230 bp upstream of exon 1 (containing a putative AP-2 and putative Sp1 binding sites) is of functional importance for SPRN transcription. Six mutations in the SPRN promoter were also found to alter the promoter activity in vitro. However, no association between any of these promoter mutations and susceptibility for classical scrapie was found.

Effect of walking speed on the intersegmental coordination of lower-limb segments in elderly adults.

BACKGROUND: Ageing brings profound changes in walking gait. For example, older adults reduce the modification of pelvic and trunk kinematics with walking speed. However, the modification of the coordination between lower-limb segments with age has never been investigated across various controlled speeds. RESEARCH QUESTION: Is the effect of speed on the intersegmental coordination different between elderly and young adults? METHODS: Nineteen senior and eight young adults walked on a treadmill at speeds ranging from 0.56 to 1.94 m s-1. The motion of the lower-limb segments in the sagittal plane was recorded by cinematography. When the angles of the thigh, shank and foot during a stride are plotted one versus the other, they describe loops constraint on a plane. The coordination between lower-limb segments was thus evaluated by performing a principal component analysis between the thigh, shank and foot elevation angles. The effect of speed and age on the intersegmental coordination was examined using a two-level linear mixed model ANOVA. RESULTS: In both age groups the orientation of the plane changes with speed, due to a more in-phase shank and foot motion. However, the effect of speed on the covariation plane is lessened with age. SIGNIFICANCE: Our results demonstrate that there is an age-related specific adjustment of the intersegmental coordination to speed. In particular, older adults restrict their repertoire of angular segment motion. These differences in coordination are mainly related to different foot-shank coordination.

Human motor control of landing from a drop in simulated microgravity.

Landing on the ground on one's feet implies that the energy gained during the fall be dissipated. The aim of this study is to assess human motor control of landing in different conditions of fall initiation, simulated gravity, and sensory neural input. Six participants performed drop landings using a trapdoor system and landings from self-initiated counter-movement jumps in microgravity conditions simulated in a weightlessness environment by different pull-down forces of 1-, 0.6-, 0.4-, and 0.2 g External forces applied to the body, orientation of the lower limb segments, and muscular activity of 6 lower limb muscles were recorded synchronously. Our results show that 1) subjects are able to land and stabilize in all experimental conditions; 2) prelanding muscular activity is always present, emphasizing the capacity of the central nervous system to approximate the instant of touchdown; 3) the kinetics and muscular activity are adjusted to the amount of energy gained during the fall; 4) the control of landing seems less finely controlled in drop landings as suggested by higher impact forces and loading rates, plus lower mechanical work done during landing for a given amount of energy to be dissipated. In conclusion, humans seem able to adapt the control of landing according to the amount of energy to be dissipated in an environment where sensory information is altered, even under conditions of non-self-initiated falls.

Motor control of landing from a countermovement jump in simulated microgravity.

Landing from a jump implies proper positioning of the lower limb segments and the generation of an adequate muscular force to cope with the imminent collision with the ground. This study assesses how a hypogravitational environment affects the control of landing after a countermovement jump (CMJ). Eight participants performed submaximal CMJs on Earth (1-g condition) and in a weightlessness environment with simulated gravity conditions generated by a pull-down force (1-, 0.6-, 0.4-, and 0.2-g0 conditions). External forces applied to the body, movements of the lower limb segments, and muscular activity of six lower limb muscles were recorded. 1) All subjects were able to jump and stabilize their landing in all experimental conditions, except one subject in 0.2-g0 condition. 2) The mechanical behavior of lower limb muscles switches during landing from a stiff spring to a compliant spring associated with a damper. This is true whatever the environment, on Earth as well as in environments where sensory inputs are altered. 3) The motor control of landing in simulated 1 g0 reveals an increased "safety margin" strategy, illustrated by increased stiffness and damping coefficient compared with landing on Earth. 4) The motor command is adjusted to the task constraints: muscular activity of lower limb extensors and flexors, stiffness and damping coefficient decrease according to the decreased gravity level. Our results show that even if in daily living gravity can be perceived as a constant factor, subjects can cope with altered sensory signals, taking advantage of the remaining information (visual and/or decreased proprioceptive inputs).

Influenza-binding sialylated polymer coated gold nanoparticles prepared via RAFT polymerization and reductive amination.

We report on a straightforward strategy to fabricate bioactive glycosylated gold nanoparticles via a combination of RAFT polymerization, carbohydrate ligation through reductive amination and thiol-gold self-assembly. This approach is used for the design of gold nanoparticles decorated with the complex sialylated glycan Neu5Ac-α-2-6-Gal, and we demonstrate multivalent and specific recognition between the nanoparticles, lectins and hemagglutinin on the surface of the influenza virus.

Leg stiffness and joint stiffness while running to and jumping over an obstacle.

During running, muscles of the lower limb act like a linear spring bouncing on the ground. When approaching an obstacle, the overall stiffness of this leg-spring system (k(leg)) is modified during the two steps preceding the jump to enhance the movement of the center of mass of the body while leaping the obstacle. The aim of the present study is to understand how k(leg) is modified during the running steps preceding the jump. Since k(leg) depends on the joint torsional stiffness and on the leg geometry, we analyzed the changes in these two parameters in eight subjects approaching and leaping a 0.65 m-high barrier at 15 km h(-1). Ground reaction force (F) was measured during 5-6 steps preceding the obstacle using force platform and the lower limb movements were recorded by camera. From these data, the net muscular moment (M(j)), the angular displacement (θ(j)) and the lever arm of F were evaluated at the hip, knee and ankle. At the level of the hip, the M(j)-θ(j) relation shows that muscles are not acting like torsional springs. At the level of the knee and ankle, the M(j)-θ(j) relation shows that muscles are acting like torsional springs: as compared to steady-state running, the torsional stiffness k(j) decreases from ~1/3 two contacts before the obstacle, and increases from ~2/3 during the last contact. These modifications in k(j) reflect in changes in the magnitude of F but also to changes in the leg geometry, i.e. in the lever arms of F.

Natural and long-lasting cellular immune responses against influenza in the M2e-immune host.

Influenza is a global health concern. Licensed influenza vaccines induce strain-specific virus-neutralizing antibodies but hamper the induction of possibly cross-protective T-cell responses upon subsequent infection.(1) In this study, we compared protection induced by a vaccine based on the conserved extracellular domain of matrix 2 protein (M2e) with that of a conventional whole inactivated virus (WIV) vaccine using single as well as consecutive homo- and heterosubtypic challenges. Both vaccines protected against a primary homologous (with respect to hemagglutinin and neuraminidase in WIV) challenge. Functional T-cell responses were induced after primary challenge of M2e-immune mice but were absent in WIV-vaccinated mice. M2e-immune mice displayed limited inducible bronchus-associated lymphoid tissue, which was absent in WIV-immune animals. Importantly, M2e- but not WIV-immune mice were protected from a primary as well as a secondary, severe heterosubtypic challenge, including challenge with pandemic H1N1 2009 virus. Our findings advocate the use of infection-permissive influenza vaccines, such as those based on M2e, in immunologically naive individuals. The combined immune response induced by M2e-vaccine and by clinically controlled influenza virus replication results in strong and broad protection against pandemic influenza. We conclude that the challenge of the M2e-immune host induces strong and broadly reactive immunity against influenza virus infection.

Adjustments after an ankle dorsiflexion perturbation during human running.

In this study we investigated the effect of a mechanical perturbation of unexpected timing during human running. With the use of a powered exoskeleton, we evoked a dorsiflexion of the right ankle during its swing phase while subjects ran on a treadmill. The perturbation resulted in an increase of the right ankle dorsiflexion of at least 5°. The first two as well as the next five steps after the perturbation were analyzed to observe the possible immediate and late biomechanical adjustments. In all cases subjects continued to run after the perturbation. The immediate adjustments were the greatest and the most frequent when the delay between the right ankle perturbation and the subsequent right foot touch-down was the shortest. For example, the vertical impact peak force was strongly modified on the first step after the perturbations and this adjustment was correlated to a right ankle angle still clearly modified at touch-down. Some late adjustments were observed in the subsequent steps predominantly occurring during left steps. Subjects maintained the step length and the step period as constant as possible by adjusting other step parameters in order to avoid stumbling and continue running at the speed imposed by the treadmill. To our knowledge, our experiments are the first to investigate perturbations of unexpected timing during human running. The results show that humans have a time-dependent, adapted strategy to maintain their running pattern.

Effect of load and speed on the energetic cost of human walking.

It is well established that the energy cost per unit distance traveled is minimal at an intermediate walking speed in humans, defining an energetically optimal walking speed. However, little is known about the optimal walking speed while carrying a load. In this work, we studied the effect of speed and load on the energy expenditure of walking. The O(2) consumption and CO(2) production were measured in ten subjects while standing or walking at different speeds from 0.5 to 1.7 m s(-1) with loads from 0 to 75% of their body mass (M(b)). The loads were carried in typical trekker's backpacks with hip support. Our results show that the mass-specific gross metabolic power increases curvilinearly with speed and is directly proportional to the load at any speed. For all loading conditions, the gross metabolic energy cost (J kg(-1) m(-1)) presents a U-shaped curve with a minimum at around 1.3 m s(-1). At that optimal speed, a load up to 1/4 M(b) seems appropriate for long-distance walks. In addition, the optimal speed for net cost minimization is around 1.06 m s(-1) and is independent of load.

Auditory startle (audio-spinal) reaction in normal man: EMG responses and H reflex changes in antagonistic lower limb muscles.

The audiospinal reaction (ASR) to a 30 msec tone of 90 dB has been studied in 66 seated healthy volunteers. Electromyographic bursts induced in trapezius (Tra), soleus (Sol) and tibialis anterior (TA) have been looked for. Facilitation of Sol H reflex has been measured in 21 subjects in terms of delays from delivery of the sound. Among the subjects, 11 had a stable TA H reflex whose facilitation was compared to that of Sol H. Effects of selective isometric voluntary contraction of either Sol or TA were assessed both on EMG responses and H reflex facilitation. At rest, only 36% of subjects exhibited a response in Sol at a mean latency of 123 msec and 39% in TA at a latency of 119 msec. Responses were seen in antagonist muscles in 74% of subjects. Incidence in Tra was 96%. During voluntary contraction, the results were not significantly changed either in the contracted muscle or its antagonist. H reflex facilitation of both TA and Sol started 50 msec after the sound to peak after 75-125 msec and returned to baseline values after 250 msec. Extent of Sol H reflex facilitation remained similar during voluntary contraction of Sol and TA. It was observed that EMG responses were more frequent in subjects with brisk reflexes but not necessarily in those who exhibited the largest H reflex facilitation. The results are in agreement with assumptions that ASR is mediated through reticulo-spinal pathways but do not support the view that it corresponds to a flexor reaction. In addition to providing quantitative data for comparisons in pathological cases, they suggest differences in the mode of activation of motoneurones by the motor cortex and subcortical nuclei.

Modifications of audio-spinal facilitation during gait in normal man.

An unexpected loud sound--sufficient to elicit an audio-spinal response in lower limb muscles during standing--has been delivered during the gait cycle in 40 healthy volunteers. Raw EMG bursts were recorded in the right trapezius (Tra), and in soleus (Sol) and tibialis anterior (TA) muscles bilaterally before being converted into envelope curves which were measured. The results indicated that the step cycle was not modified. On the other hand, EMG bursts time-locked to the sound appeared in Tra during gait. Audio-spinal responses similar to those seen during standing were present during gait only in the flexor TA provided it was silent. In Sol, responses were absent regardless of whether it was active or not. Some later and not time-locked EMG reinforcements were however seen, provided Sol was active. The audio-spinal responses during gait differed thus markedly from those seen at rest in the standing position. It is suggested to consider intervention of the central pattern generator which is already known to alter dramatically the responses to peripheral stimuli during gait. Another possibility might be that the descending influences are modified in supraspinal structures but this interpretation is less likely as responses are not cyclically modified in Tra.

The mechanics of running in children.

1. The effect of age and body size on the bouncing mechanism of running was studied in children aged 2-16 years. 2. The natural frequency of the bouncing system (fs) and the external work required to move the centre of mass of the body were measured using a force platform. 3. At all ages, during running below approximately 11 km h-1, the freely chosen step frequency (f) is about equal to fs (symmetric rebound), independent of speed, although it decreases with age from 4 Hz at 2 years to 2.5 Hz above 12 years. 4. The decrease of step frequency with age is associated with a decrease in the mass-specific vertical stiffness of the bouncing system (k/m) due to an increase of the body mass (m) with a constant stiffness (k). Above 12 years, k/m and f remain approximately constant due to a parallel increase in both k and m with age. 5. Above the critical speed of approximately 11 km h-1, independent of age, the rebound becomes asymmetric, i.e. f < fs. 6. The maximum running speed (Vf, max) increases with age while the step frequency at remains constant (approximately 4 Hz), independent of age. 7. At a given speed, the higher step frequency in preteens results in a mass-specific power against gravity less than that in adults. The external power required to move the centre of mass of the body is correspondingly reduced.

The double contact phase in walking children.

During walking, when both feet are on the ground (the double contact phase), the legs push against each other, and both positive and negative work are done simultaneously. The work done by one leg on the other (W(int,dc)) is not counted in the classic measurements of the positive muscular work done during walking. Using force platforms, we studied the effect of speed and age (size) on W(int,dc). In adults and in 3-12-year-old children, W(int,dc) (J kg(-1) m(-1)) as a function of speed shows an inverted U-shaped curve, attaining a maximum value that is independent of size but that occurs at higher speeds in larger subjects. Normalising the speed with the Froude number shows that W(int,dc) is maximal at about 0.3 in both children and adults. Differences due to size disappear for the most part when normalised with the Froude number, indicating that these speed-dependent changes are primarily a result of body size changes. At its maximum, W(int,dc) represents more than 40% of W(ext) (the positive work done to move the centre of mass of the body relative to the surroundings) in both children and adults.

Mechanical work and muscular efficiency in walking children.

The effect of age and body size on the total mechanical work done during walking is studied in children of 3-12 years of age and in adults. The total mechanical work per stride (W tot) is measured as the sum of the external work, W ext (i.e. the work required to move the centre of mass of the body relative to the surroundings), and the internal work, W int (i.e. the work required to move the limbs relative to the centre of mass of the body, W int,k, and the work done by one leg against the other during the double contact period, W int,dc). Above 0.5 m s(-1), both W ext) and W int,k, normalised to body mass and per unit distance (J kg(-1) m(-1)), are greater in children than in adults; these differences are greater the higher the speed and the younger the subject. Both in children and in adults, the normalised W int,dc shows an inverted U-shape curve as a function of speed, attaining a maximum value independent of age but occurring at higher speeds in older subjects. A higher metabolic energy input (J kg(-1) m(-1)) is also observed in children, although in children younger than 6 years of age, the normalised mechanical work increases relatively less than the normalised energy cost of locomotion. This suggests that young children have a lower efficiency of positive muscular work production than adults during walking. Differences in normalised mechanical work, energy cost and efficiency between children and adults disappear after the age of 10.