The social position of male Barbary macaques (Macaca sylvanus) in a semifree-ranging population

A study was carried out on the social position of 12 subadult males of a semifreeranging Barbary macaque population during the non-mating season. The social position was measured in terms of spatial as well as interactive parameters. The subadult males had social contacts to members of nearly all other age-sex classes but showed clear preferences for same-sexed partners. Besides this differences were found between 5- and 6-year-old males with respect to their interaction profiles and the preference for special classes of interaction partners. The terms “peripheral-central” is discussed with reference to the social structures of macaque societies. The data of the present study indicate that the social position of subadult male Barbary macaques can not be described by one of these terms exclusively. The results are compared to other studies on Barbary macaques and other macaque species. It is concluded that in macaque societies subadult males are not obligatorily forced to live at the periphery or to abide. It is proposed not to postulate stiff social structures but to put more emphasis on the range of variation among macaque species.     

The mechanical microenvironment of high concentration agarose for applying deformation to primary chondrocytes

Cartilage and chondrocytes experience loading that causes alterations in chondrocyte biological activity. In vivo chondrocytes are surrounded by a pericellular matrix with a stiffness of ~25–200 kPa. Understanding the mechanical loading environment of the chondrocyte is of substantial interest for understanding chondrocyte mechanotransduction. The first objective of this study was to analyze the spatial variability of applied mechanical deformations in physiologically stiff agarose on cellular and sub-cellular length scales. Fluorescent microspheres were embedded in physiologically stiff agarose hydrogels. Microsphere positions were measured via confocal microscopy and used to calculate displacement and strain fields as a function of spatial position. The second objective was to assess the feasibility of encapsulating primary human chondrocytes in physiologically stiff agarose. The third objective was to determine if primary human chondrocytes could deform in high-stiffness agarose gels. Primary human chondrocyte viability was assessed using live–dead imaging following 24 and 72 h in tissue culture. Chondrocyte shape was measured before and after application of 10% compression. These data indicate that (1) displacement and strain precision are ~1% and 6.5% respectively, (2) high-stiffness agarose gels can maintain primary human chondrocyte viability of >95%, and (3) compression of chondrocytes in 4.5% agarose can induce shape changes indicative of cellular compression. Overall, these results demonstrate the feasibility of using high-concentration agarose for applying in vitro compression to chondrocytes as a model for understanding how chondrocytes respond to in vivo loading.     

The effect of test methodology on apparent compressive stiffness of tibiofemoral joint specimens

Several investigators have analysed the compressive load bearing properties of the knee. Careful review of these force/displacement data showed considerable variation, with some investigators reporting displacements 12-15 x higher than others for nearly identical testing conditions using the same animal model. In this study, we sought to determine if this variability was inherent in the tibiofemoral joint or if differences in experimental methodology explained the variation. Compressive force/displacement curves were obtained from 39 normal canine tibiofemoral specimens mounted in a universal testing machine. Two commonly reported methods of measuring compressive displacement were used simultaneously. The testing machine crosshead displacement was used as one measure of displacement of the joint. The other method consisted of extensometers mounted to bone at the joint line. Resultant joint rotation in the parasagittal plane was also measured. Using either approach, we found comparatively little variation among the 39 specimens tested. However, the crosshead displacement measurements diverged from the extensometer measurements as the compressive load increased. At 770 N, the crosshead measurement was nearly twice the extensometer displacement. Further analysis showed that the compliances differed by a uniform amount. Parasagittal joint rotation, as measured by the extensometers, was minimal--less than one half of one degree. Although our loading fixtures were expected to be rigid under the loads used, these data suggest that the deformation of the bone and loading fixtures was responsible for the differences we observed, and may be responsible for the variation in compressive displacement results among several published studies. A model is presented which uses a simple elastic element to represent this deformation.     

An investigation of the mechanisms of eye movement control

Summary Feedback mechanisms exist in all the periferal sense organs including the eye, which acts as a highly efficient position control servo system. Histological studies so far have not revealed the precise circuitry of the eye movement control system but some information about it can be obtained by a study of the sources of feedback. Existing theories have considered three types of feedback originating in the oculomotor tract, in the proprioceptive fibres of the extrinsic eye muscles and from retinal image displacement. In the present experiments an optical arrangement has been used to vary or eliminate the amount of information available from retinal image motion, and the response of the eye to simple harmonic displacement of a target has been recorded. The response curves of gain (eyeball movement divided by target motion) against frequency indicate that the system is lion linear when the image falls in the retinal region which is insensitive to position. Outside this area, retinal image position is used as negative feedback but the information from the oculomotor tract must be regenerative. There is also evidence for feedback proportional to the first derivative of eyeball position and this function is ascribed to the proprioceptive signals; this form of feedback appears to saturate for large amplitude movements, thus avoiding heavy damping of the flick movements.A schematic eye movement control system having the same characteristics as the eye is proposed. The transfer function of this system indicates that it should be unstable if the sign of the retinal image feedback loop is reversed. Experiments with this form of feedback show that steady fixation is impossible and the eye performs a pendular nystagmus.     

The effects of plaque morphology and material properties on peak cap stress in human coronary arteries

Heart attacks are often caused by rupture of caps of atherosclerotic plaques in coronary arteries. Cap rupture occurs when cap stress exceeds cap strength. We investigated the effects of plaque morphology and material properties on cap stress. Histological data from 77 coronary lesions were obtained and segmented. In these patient-specific cross sections, peak cap stresses were computed by using finite element analyses. The finite element analyses were 2D, assumed isotropic material behavior, and ignored residual stresses. To represent the wide spread in material properties, we applied soft and stiff material models for the intima. Measures of geometric plaque features for all lesions were determined and their relations to peak cap stress were examined using regression analyses. Patient-specific geometrical plaque features greatly influence peak cap stresses. Especially, local irregularities in lumen and necrotic core shape as well as a thin intima layer near the shoulder of the plaque induce local stress maxima. For stiff models, cap stress increased with decreasing cap thickness and increasing lumen radius (R = 0.79). For soft models, this relationship changed: increasing lumen radius and increasing lumen curvature were associated with increased cap stress (R = 0.66). The results of this study imply that not only accurate assessment of plaque geometry, but also of intima properties is essential for cap stress analyses in atherosclerotic plaques in human coronary arteries.     

The P1 phage replication protein RepA contacts an otherwise inaccessible thymine N3 proton by DNA distortion or base flipping

The RepA protein from bacteriophage P1 binds DNA to initiate replication. RepA covers one face of the DNA and the binding site has a completely conserved T that directly faces RepA from the minor groove at position +7. Although all four bases can be distinguished through contacts in the major groove of B-form DNA, contacts in the minor groove cannot easily distinguish between A and T bases. Therefore the 100% conservation at this position cannot be accounted for by direct contacts approaching into the minor groove of B-form DNA. RepA binding sites with modified base pairs at position +7 were used to investigate contacts with RepA. The data show that RepA contacts the N3 proton of T at position +7 and that the T=A hydrogen bonds are already broken in the DNA before RepA binds. To accommodate the N3 proton contact the T₊₇ /A_+7^′ base pair must be distorted. One possibility is that T₊₇ is flipped out of the helix. The energetics of the contact allows RepA to distinguish between all four bases, accounting for the observed high sequence conservation. After protein binding, base pair distortion or base flipping could initiate DNA melting as the second step in DNA replication.     

Cell wall structure and mechanical properties of Phycomyces

The cell wall of the sporangiophore of the fungus Phycomyces is modeled assuming the primary microstructural elements consist of stiff chitin microfibrils embedded in a Newtonian viscous matrix. The structural parameters of the model are estimated from scanning electron micrographs taken of the inside of the growth zone of the sporangiophore, published X-ray data and published transmission electron micrographs of the cell wall. The plastic extension rate normalized with respect to imposed crosshead speed is calculated from the model and compared to measured rates obtained from a tensile test. Reasonable agreement is observed for the most natural choice of the microstructural parameters employed in the model.     

The application of kinematic equations for the study of cell turnover

Cell turnover in renewing populations is accompanied by cell displacement from a site where cells are formed to a location where they are eliminated. Cell displacement reflects genuine streaming, proceeding along a trajectory denominated as tissue radius. In the sagittally sectioned gastro-intestinal crypt the radius extends along one of its cell columns. In each column the cell locations are numbered so that the crypt origin resides at location 1. Since the cell proceeds from the first location and outward, given two locations i and j such that j greater than i, the cell at j is older or more differentiated than the cell at location i, or more generally, state j represents the future state of i while state i represents a past stage for j. Cell displacement on the radius depends solely upon cell production and the acceleration of a cell through location i equals the cell production rate there. Its velocity may be represented by kinematic equations which in the present context acquire dual meaning: either describing cell displacement, or cell production associated with cell displacement. Cell velocities may be derived by following a labelled cell with time or from density distributions of labelled cells along the tissue radius. The first approach is essentially kinematic, while the second regards the density distribution as an analog of mechanical work and since work involves displacement, velocity (and cell production) is derivable from the density distribution. The two estimates are denominated here as time and space estimates. The second approach is essentially morphological, and may be applied during routine examination of histopathological slide and even be computerized.(ABSTRACT TRUNCATED AT 250 WORDS)     

Potentiometric titration of polyelectrolytes having stiff backbones

The potentiometric titration curves of carboxymethylcellulose, which has a relatively stiff backbone, and also of poly(D -glutamic acid) in the helical region are compared with the theoretical curves calculated assuming that the polyions are rods and have smeared charges on their surfaces. For carboxymethylcellulose good agreement is observed when its charge density is high, whereas as the charge density decreases the calculated curves deviate from the observed ones. The main reason for the disagreement at low charge densities may be attributed to the flexibility of the polymer backbone. For helical poly(D -glutamic acid) satisfactory agreement between calculated and observed curves is found if a radius thicker than the realistic radius is employed. The reason for the excessively large radius may be attributed to the inapplicability of the smeared charge model.     

An atomic resolution structure for human fibroblast growth factor 1

A 1.10-A atomic resolution X-ray structure of human fibroblast growth factor 1 (FGF-1), a member of the beta-trefoil superfold, has been determined. The beta-trefoil is one of 10 fundamental protein superfolds and is the only superfold to exhibit 3-fold structural symmetry (comprising 3 "trefoil" units). The quality of the diffraction data permits unambiguous assignment of Asn, Gln, and His rotamers, Pro ring pucker, as well as refinement of atomic anisotropic displacement parameters (ADPs). The FGF-1 structure exhibits numerous core-packing defects, detectable using a 1.0-A probe radius. In addition to contributing to the relatively low thermal stability of FGF-1, these defects may also permit domain motions within the structure. The availability of refined ADPs allows a translation/libration/screw (TLS) analysis of putative rigid body domains. The TLS analysis shows that beta-strands 6-12 together form a rigid body, and there is a clear demarcation in TLS motions between the adjacent carboxyl- and amino-termini. Although separate from beta-strands 6-12, the individual beta-strands 1-5 do not exhibit correlated motions; thus, this region appears to be comparatively flexible. The heparin-binding contacts of FGF-1 are located within beta-strands 6-12; conversely, a significant portion of the receptor-binding contacts are located within beta-strands 1-5. Thus, the observed rigid body motion in FGF-1 appears related to the ligand-binding functionalities.     

Contact guidance in vitro : A light, transmission, and scanning electron microscopic study

Contact guidance was studied in cultures of chick heart fibroblasts and kidney epithelium by observing the relation of these cells to fine grooves ruled in plastic culture dishes, and also to ridges or grooves in plastic replicas moulded from rulings made in metal. The relation of the cells to the regularly arranged collagen fibers of fish scales was also studied by scanning and transmission electron microscopy (SEM and TEM). On the rulings with groove periodicity in the range of 5 μm about 75% of the cells were aligned, but on grooves separated about 30 μm only 60% of cells were aligned. Cytoplasmic components of the cells such as microfilaments maintained a constant relation to the axis of the cell as a whole, but they, and also any cytoplasmic extensions, such as filopodia, bore no consistent relation to any features of the substratum, whether or not the cells were aligned. The cells were not guided to become aligned by filopodia or lamellipodia. The most remarkable and consistent finding was that cells bridged over grooves without contacting their surfaces, whether the grooves were 2 or 10 μm wide. The bridging was a characteristic of cells growing on any of the substrates, including those with grooves or ridges, and also of collagen substrates made from fish scales. A hypothesis is proposed to explain the contact guidance seen on ridged or grooved substrata and on the orientated collagen fibers involving the observed cell bridging and the fact that linear cell-to-substrate contacts (focal contacts) are known to be vital for cell movement. The cell is considered to be stiff so that as it bridges over much of the substratum there is only a limited area available for contact. Assuming that focal contacts need to be of a certain length to provide adhesion, a cell orientation that presents the maximum linear contact would be favoured. An examination of the results of this study and of the reports in the literature shows that cells on these types of substrata take on an orientation such that linear contacts would be expected to predominate.     

RhoA is down-regulated at cell–cell contacts via p190RhoGAP-B in response to tensional homeostasis

Breast epithelial cells cultured in three-dimensional (3D) collagen gels undergo ductal morphogenesis when the gel is compliant and they can achieve tensional homeostasis. We previously showed that this process requires down-regulation of Rho in compliant collagen gels, but the mechanism remains undefined. In this study, we find that p190RhoGAP-B, but not p190RhoGAP-A, mediates down-regulation of RhoA activity and ductal morphogenesis in T47D cells cultured in compliant 3D collagen gels. In addition, both RhoA and p190RhoGAP-B colocalize with p120-catenin at sites of cell–cell contact. The association between p190RhoGAP-B and p120-catenin is regulated by matrix compliance such that it increases in compliant vs. rigid collagen gels. Furthermore, knockdown of p120-catenin disrupts ductal morphogenesis, disregulates RhoA activity, and results in loss of p190B at cell–cell contacts. Consistent with these findings, using a RhoA-specific FRET biosensor (RhoA-FLARE.sc), we determined spatial RhoA activity to be significantly decreased at cell–cell contacts versus cell–ECM adhesions, and, of importance, spatial RhoA activity is regulated by p190B. This finding suggests that RhoA exists as an inactive pool at cell–cell contacts and is recruited to cell–ECM contacts within stiff matrices. Overall, these results demonstrate that RhoA is down-regulated at cell–cell contacts through p190RhoGAP-B, which is localized to cell–cell contacts by association with p120-catenin that is regulated by tensional homeostasis.     

Kinematics of soft-bodied, legged locomotion in Manduca sexta larvae

Caterpillar crawling is distinct from that of worms and molluscs; it consists of a series of steps in different body segments that can be compared to walking and running in animals with stiff skeletons. Using a three-dimensional kinematic analysis of horizontal crawling in Manduca sexta, the tobacco hornworm, we found that the phase of vertical displacement in the posterior segments substantially led changes in horizontal velocity and the segments appeared to pivot around the attached claspers. Both of the motions occur during vertebrate walking. In contrast, vertical displacement and horizontal velocity in the anterior proleg-bearing segments were in phase, as expected for running gaits coupled by elastic storage. We propose that this kinematic similarity to running results from the muscular compression and release of elastic tissues. As evidence in support of this proposal, the compression and extension of each segment were similar to harmonic oscillations in a spring, although changes in velocity were 70 degrees out of phase with displacement, suggesting that the spring was damped. Measurements of segment length within, and across, intersegmental boundaries show that some of these movements were caused by folding of the body wall between segments. These findings demonstrate that caterpillar crawling is not simply the forward progression of a peristaltic wave but has kinetic components that vary between segments. Although these movements can be compared to legged locomotion in animals with stiff skeletons, the underlying mechanisms of caterpillar propulsion, and in particular the contribution of elastic tissues, remain to be discovered.     

Not all types of host contacts are equal when it comes to E. coli transmission

The specific processes that facilitate pathogen transmission are poorly understood, particularly for wild animal populations. A major impediment for investigating transmission pathways is the need for simultaneous information on host contacts and pathogen transfer. In this study, we used commensal Escherichia coli strains as a model system for gastrointestinal pathogens. We combined strain‐sharing information with detailed host contact data to investigate transmission routes in mountain brushtail possums. Despite E. coli being transmitted via the faecal‐oral route, we revealed that, strain‐sharing among possums was better explained by host contacts than spatial proximity. Furthermore, and unexpectedly, strain‐sharing was more strongly associated with the duration of brief nocturnal associations than day‐long den‐sharing. Thus, the most cryptic and difficult associations to measure were the most relevant connections for the transmission of this symbiont. We predict that future studies that employ similar approaches will reveal the importance of previously overlooked associations as key transmission pathways.     

Low impedance walking robots

For both historical and technological reasons, most robots,including those meant to mimic animals or operate in naturalenvironments,³ use actuators and control systems that have high(stiff) mechanical impedance. By contrast, most animals exhibitlow (soft) impedance. While a robot's stiff joints may be programmedto closely imitate the recorded motion of an animal's soft joints,any unexpected position disturbances will generate reactiveforces and torques much higher for the robot than for the animal.The dual of this is also true: while an animal will react toa force disturbance by significantly yielding position, a typicalrobot will greatly resist. These differences cause three deleterious effects for high impedancerobots. First, the higher forces may cause damage to the robotor to its environment (which is particularly important if thatenvironment includes people). Second, the robot must acquirevery precise information about its position relative to theenvironment so as to minimize its velocity upon impact. Third,many of the self-stabilizing effects of natural dynamics are"shorted out"⁴ by the robot's high impedance, so that stabilizationrequires more effort from the control system. Over the past 5 yr, our laboratory has designed a series ofwalking robots based on "Series-Elastic Actuators" and "VirtualModel Control." Using these two techniques, we have been ableto build low-impedance walking robots that are both safe androbust, that operate blindly without any model of upcoming terrain,and that add minimal control effort in parallel to their self-stabilizingpassive dynamics. We have discovered that it is possible toachieve surprisingly effective ambulation from rather simplemechanisms and control systems. After describing the historicaland technological motivations for our approach, this paper givesan overview of our methods and shows some of the results wehave obtained.     

Radius of gyration is indicator of compactness of protein structure

Search and study of the general principles that govern kinetics and thermodynamics of protein folding generate a new insight into the factors controlling this process. Statistical analysis of radii of gyration for 3769 protein structures from four general structural classes (all-alpha, all-beta, alpha/beta, alpha + beta) demonstrates that each class of proteins has its own class-specific radius of gyration, which determines compactness of protein structures: alpha-proteins have the largest radius of gyration. This indicates that they are less tightly packed than beta- and alpha + beta-proteins. Finally, alpha/beta-proteins are the most tightly packed proteins with the least radius of gyration. It should be underlined that radius of gyration normalized on the radius of gyration of ball with the same volume, is independent of the length in comparison with such parameters as compactness and number of contacts per residue.     

Differential displacement of the human soleus and medial gastrocnemius aponeuroses during isometric plantar flexor contractions in vivo.

The human triceps surae muscle-tendon complex is a unique structure with three separate muscle compartments that merge via their aponeuroses into the Achilles tendon. The mechanical function and properties of these structures during muscular contraction are not well understood. The purpose of the study was to investigate the extent to which differential displacement occurs between the aponeuroses of the medial gastrocnemius (MG) and soleus (Sol) muscles during plantar flexion. Eight subjects (mean +/- SD; age 30 +/- 7 yr, body mass 76.8 +/- 5.5 kg, height 1.83 +/- 0.06 m) performed maximal isometric ramp contractions with the plantar flexor muscles. The experiment was performed in two positions: position 1, in which the knee joint was maximally extended, and position 2, in which the knee joint was maximally flexed (125 degrees ). Plantarflexion moment was assessed with a strain gauge load cell, and the corresponding displacement of the MG and Sol aponeuroses was measured by ultrasonography. Differential shear displacement of the aponeurosis was quantified by subtracting displacement of Sol from that of MG. Maximal plantar flexion moment was 36% greater in position 1 than in position 2 (132 +/- 20 vs. 97 +/- 11 N.m). In position 1, the displacement of the MG aponeurosis at maximal force exceeded that of the Sol (12.6 +/- 1.7 vs. 8.9 +/- 1.5 mm), whereas in position 2 displacement of the Sol was greater than displacement of the MG (9.6 +/- 1.0 vs. 7.9 +/- 1.2 mm). The amount and "direction" of shear between the aponeuroses differed significantly between the two positions across the entire range of contraction, indicating that the Achilles tendon may be exposed to intratendinous shear and stress gradients during human locomotion.     

Optimal shear cushion stiffness at different gait speeds

The present study quantified the effects of different shear cushion stiffness on the time to peak posterior shear force (TPPSF), peak posterior shear force (PPSF), average posterior loading rate (APLR), and maximum posterior loading rate (MPLR) at different locomotion speeds using a custom-made sliding platform, as well as to identify the optimal stiffness of shear cushion. Twelve male collegiate students (heel-strikers) performed walking at 1.5 m/s, jogging at 2.5 m/s, and running at 3.5 m/s. A custom-made sliding platform was used to provide the different shear cushion conditions. The shear cushion conditions were fixed (a fixed platform; control group), stiff (K = 2746 N/m), medium stiff (K = 2256 N/m), medium soft (K = 1667 N/m), and soft (K = 1079 N/m). The results showed that all cushion conditions produced sliding displacement and delayed the TPPSF during walking, jogging, and running compared with fixed condition. The APLR and MPLR were lowest under medium soft condition during walking, while the PPSF was similar between medium soft and soft conditions. For jogging and running, the PPSF as well as APLR and MPLR were the lowest under medium stiff condition except the maximum PLR was similar among stiff, medium stiff, and medium soft conditions during running. In conclusion, shear cushion produces appropriate sliding displacement and effectively delays the TPPSF to provide the musculoskeletal system additional time to absorb the impact and reduce loading. The present study demonstrates optimal stiffness of shear cushion at different traveling speeds and suggests that a shear cushion system can be applied in future designs of cushion structures.     

On the progenitor cell migration velocity

An attempt is presented to extract cell kinetic information from histomorphological features. It is applicable to rapidly proliferating tissues like the intestinal epithelium. Each replicating tissue has an origin where cells are formed and a periphery toward which cells migrate. The migration path along which they move is denominated as tissue radius on which all cell positions are mapped. Cell migration on the radius is associated with cell proliferation at tissue origin. Each mitosis there is associated with the displacement of all cells distal to it by one cell position. The more mitoses positioned between a cell and tissue origin, the greater its migration velocity. It is possible therefore to derive the cell migration velocity v(x) from the cumulative mitotic distribution on the radius, N(x). v(x) = N(x)/tm (tm = mitotic time). In this form v(x) represents also cell production at any point on the radius and may serve for the computation of other cell kinetic parameters like generation time. These arguments are illustrated on the rat incisor tooth inner enamel epithelium which has been studied in the normal and rapidly erupting tooth.