Comparison of the elastic and yield properties of human femoral trabecular and cortical bone tissue

The ability to determine trabecular bone tissue elastic and failure properties has biological and clinical importance. To date, trabecular tissue yield strains remain unknown due to experimental difficulties, and elastic moduli studies have reported controversial results. We hypothesized that the elastic and tensile and compressive yield properties of trabecular tissue are similar to those of cortical tissue. Effective tissue modulus and yield strains were calibrated for cadaveric human femoral neck specimens taken from 11 donors, using a combination of apparent-level mechanical testing and specimen-specific, high-resolution, nonlinear finite element modeling. The trabecular tissue properties were then compared to measured elastic modulus and tensile yield strain of human femoral diaphyseal cortical bone specimens obtained from a similar cohort of 34 donors. Cortical tissue properties were obtained by statistically eliminating the effects of vascular porosity. Results indicated that mean elastic modulus was 10% lower (p<0.05) for the trabecular tissue (18.0+/-2.8 GPa) than for the cortical tissue (19.9+/-1.8 GPa), and the 0.2% offset tensile yield strain was 15% lower for the trabecular tissue (0.62+/-0.04% vs. 0.73+/-0.05%, p<0.001). The tensile-compressive yield strength asymmetry for the trabecular tissue, 0.62 on average, was similar to values reported in the literature for cortical bone. We conclude that while the elastic modulus and yield strains for trabecular tissue are just slightly lower than those of cortical tissue, because of the cumulative effect of these differences, tissue strength is about 25% greater for cortical bone.     

Fluid shear stress in trabecular bone marrow due to low-magnitude high-frequency vibration

Low-magnitude high-frequency (LMHF) loading has recently received attention for its anabolic effect on bone. The mechanism of transmission of the anabolic signal is not fully understood, but evidence indicates that it is not dependent on bone matrix strain. One possible source of signaling is mechanostimulation of the cells in the bone marrow. We hypothesized that the magnitude of the fluid shear stress in the marrow during LMHF loading is in the mechanostimulatory range. As such, the goal of this study was to determine the range of shear stress in the marrow during LMHF vibration. The shear stress was estimated from computational models, and its dependence on bone density, architecture, permeability, marrow viscosity, vibration amplitude and vibration frequency were examined. Three-dimensional finite element models of five trabecular bone samples from different anatomic sites were constructed, and a sinusoidal velocity profile was applied to the models. In human bone models during axial vibration at an amplitude of 1 g, more than 75% of the marrow experienced shear stress greater than 0.5Pa. In comparison, in vitro studies indicate that fluid induced shear stress in the range of 0.5 to 2.0Pa is anabolic to a variety of cells in the marrow. Shear stress at the bone-marrow interface was as high as 5.0Pa. Thus, osteoblasts and bone lining cells that are thought to reside on the endosteal surfaces may experience very high shear stress during LMHF loading. However, a more complete understanding of the location of the various cell populations in the marrow is needed to quantify the effects on specific cell types. This study suggests the shear stress within bone marrow in real trabecular architecture during LMHF vibration could provide the mechanical signal to marrow cells that leads to bone anabolism.     

Gastrointestinal and immunological responses of senior dogs to chicory and mannan-oligosaccharides

Thirty-four senior dogs (pointers 8 - 11 years, beagles 9 - 11 years) were used to evaluate the effects of oligosaccharides on nutritional and immunological characteristics. Dogs were randomly allotted to treatments [1% chicory (CH), 1% mannan-oligosaccharide (MOS), 1% chicory + 1% MOS (CM), or no supplementation (control, CON)] in a parallel design with a 4 week baseline period followed by a 4 week treatment period. Dietary supplementation with MOS or CM tended (P = 0.07) to increase food intake due, in part, to an increase in fermentable fibre and a decrease in energy content of the diet. Although wet faecal output increased (P < 0.05) for dogs supplemented with MOS or CM, when corrected for food intake, no differences were noted. The CM treatment increased (P < 0.05) faecal score (1 = hard and dry, 5 = watery liquid), although these scores remained in a desirable range (3 to 3.5). Chicory supplementation increased (P = 0.07) fat digestibility. Chicory or MOS increased (P  0.05) faecal bifidobacteria concentrations 0.4 and 0.5 log₁₀ cfu/g DM, respectively, compared to the CON, while MOS decreased (P < 0.05) faecal E. coli concentrations. Oligosaccharides did not affect white blood cell (WBC) concentrations, but CH and CM tended to increase (P = 0.10) neutrophil concentrations compared to control dogs. Peripheral lymphocyte concentrations were decreased in dogs supplemented with MOS (P = 0.06) and CM (P < 0.05). Chicory and MOS alter faecal microbial populations and certain indices of the immune system of senior dogs.     

Constitutive expression of IL-22 in the human intervertebral disc and its reduction by exposure to pro-inflammatory cytokines in vitro

The importance of cytokines in disc degeneration is well recognized. Little is known about IL-22 expression in the human intervertebral disc. We investigated IL-22 immuno-localization in disc tissue, and molecular expression and production of IL-22 by annulus cells cultured in three-dimensional (3D) culture. We examined human disc tissue using immunohistochemistry and we cultured isolated annulus cells in 3D to analyze IL-22 expression and production, and its receptor, IL-22R, in conditioned media. Ingenuity pathway analysis (IPA) also was used to identify significant gene expression networks within the molecular data. IL-22 and IL-22R were immunolocalized in many cells in the human outer and inner annulus; fewer cells exhibited localization in the nucleus. Three-dimensional culture of annulus cells demonstrated production of IL-22 in conditioned media; exposure to IL-1ß or TNF-α significantly reduced IL-22 levels. Significant decreases also were identified in conditioned media assayed for IL-22R in TNF-α treated cells. IPA analysis showed that IL-22 ranked among the top canonical pathways. We found constitutive expression and production of IL-22 and IL-22R in the disc, which expands our understanding of the effect of pro-inflammatory cytokines on IL-22 expression and production. Three-dimensional cultured annulus cells exposed to IL-1ß or TNF produced significantly lower levels of IL-22 into their conditioned media compared to levels produced by control cells. Our findings have clinical relevance because of the elevated pro-inflammatory milieu within the degenerating human disc.     

Dual Acylation Accounts for the Localization of α19-Giardin in the Ventral Flagellum Pair of Giardia lamblia

A Giardia-specific protein family denominated as α-giardins, represents the major protein component, besides tubulin, of the cytoskeleton of the human pathogenic parasite Giardia lamblia. One of its members, α19-giardin, carries an N-terminal sequence extension of MGCXXS, which in many proteins serves as a target for dual lipid conjugation: myristoylation at the glycine residue after removal of the methionine and palmitoylation at the cysteine residue. As the first experimental evidence of a lipid modification, we found α19-giardin to be associated with the membrane fraction of disrupted trophozoites. After heterologous coexpression of α19-giardin with giardial N-myristoyltransferase (NMT) in Escherichia coli, we found the protein in a myristoylated form. Additionally, after heterologous expression together with the palmitoyl transferase Pfa3 in Saccharomyces cerevisiae, α19-giardin associates with the membrane of the main vacuole. Immunocytochemical colocalization studies on wild-type Giardia trophozoites with tubulin provide evidence that α19-giardin exclusively localizes to the ventral pair of the giardial flagella. A mutant in which the putatively myristoylated N-terminal glycine residue was replaced by alanine lost this specific localization. Our findings suggest that the dual lipidation of α19-giardin is responsible for its specific flagellar localization.The human pathogenic parasite Giardia lamblia (syn. Giardia intestinalis), a phylogenetically basal eukaryote (41), is the causative agent of giardiasis, an intestinal disease most prevalent in developing countries (39). The protist has a simple life cycle consisting of two stages, a vegetative trophozoite dwelling in the host intestine and an infective cyst form. Proliferating trophozoites are distinguished by a complex cytoskeleton whose most striking feature are eight flagella and a ventral disk, by which the parasite attaches to the intestinal epithelium of the host (11). As a diplomonad protist, the parasite possesses four different pairs of flagella, of which only the ventral and posterolateral ones are replicated in the first round of the cell cycle; the other two pairs require two further cell divisions for their complete renewal (32).Besides tubulin, the Giardia-specific giardins account for the major protein components of the giardial cytoskeleton (7, 36). From these 30- to 45-kDa proteins, the α-giardins have been recognized, based on sequence similarities, as annexin homologues (28). They represent a multiple set of all-helical proteins distinguished by four annexin domains each. We have previously confirmed that some α-giardins, indeed, satisfy a criterion of annexins, i.e., Ca²⁺-dependent association with phospholipids (1, 13, 43). Hence, these giardins have been nominated as protozoan annexins E1 to E3 (9). However, in contrast to annexins of multicellular organisms, some α-giardins contain specific sequence motifs in the fourth annexin domain, and these motifs are located at the cytoplasmic face and may make contact between the plasma membrane and the cytoskeleton within the cell (35, 43).The genome of G. lamblia possesses a total of 21 α-giardin-encoding genes (27, 30, 47). The particular importance of their gene products for the parasite may be indicated by the following: the human genome contains only 12 annexin genes, and the genome of Saccharomyces cerevisiae has none at all. Phylogenetic analyses of the α-giardin genes revealed that 19 members of this family evolved from two widely ramified branches, whereby the genes coding for α14-giardin (annexin E1, according to the annexin nomenclature) and α19-giardin jointly form a single arm (47). α19-Giardin, the subject of the present study, carries a predicted N-terminal sequence extension with an MGCXXS motif known as a target for dual fatty acylation, i.e., myristoylation at the N-terminal glycine and palmitoylation at the cysteine residue (8). However, no experimental data for a lipid conjugation to this protein and any other giardin are currently available.In the present study, we provide the first evidence that α19-giardin indeed can be both myristoylated and palmitoylated. In contrast to α14-giardin, which we found to be located in all giardial flagella as well as in the median body of the trophozoites (43, 46), α19-giardin appears exclusively localized to the ventral flagella of the trophozoites and is restricted to those portions protruding outside the cell body.     

Scene content selected by active vision

The primate visual system actively selects visual information from the environment for detailed processing through mechanisms of visual attention and saccadic eye movements. This study examines the statistical properties of the scene content selected by active vision. Eye movements were recorded while participants free-viewed digitized images of natural and artificial scenes. Fixation locations were determined for each image and image patches were extracted around the observed fixation locations. Measures of local contrast, local spatial correlation and spatial frequency content were calculated on the extracted image patches. Replicating previous results, local contrast was found to be greater at the points of fixation when compared to either the contrast for image patches extracted at random locations or at the observed fixation locations using an image-shuffled database. Contrary to some results and in agreement with other results in the literature, a significant decorrelation of image intensity is observed between the locations of fixation and other neighboring locations. A discussion and analysis of methodological techniques is given that provides an explanation for the discrepancy in results. The results of our analyses indicate that both the local contrast and correlation at the points of fixation are a function of image type and, furthermore, that the magnitude of these effects depend on the levels of contrast and correlation present overall in the images. Finally, the largest effect sizes in local contrast and correlation are found at distances of approximately 1 deg of visual angle, which agrees well with measures of optimal spatial scale selectivity in the visual periphery where visual information for potential saccade targets is processed.     

Electrophysiological correlates of synchronous neural activity and attention: a short review

Attentional selection implies preferential treatment of some sensory stimuli over others. This requires differential representation of attended and unattended stimuli. Most previous research has focused on pure rate codes for this representation but recent evidence indicates that a mixed code, involving both mean firing rate and temporal codes, may be employed. Of particular interest is a distinction of attended from unattended stimuli based on synchrony within neural populations. I review electrophysiological evidence at macroscopic, mesoscopic and microscopic spatial scales showing that the degree of synchronous activity varies with the attentional state of the perceiving organism.     

Axial-shear interaction effects on microdamage in bovine tibial trabecular bone

Because many osteoporotic fractures occur during a fall, understanding the effect of off-axis loads on initiation and propagation of microdamage in trabecular bone should provide further insight into the biomechanics of age-related fractures. Fourteen on-axis cylindrical specimens were prepared from 12 bovine tibiae. Fluorescent stains were used to label the microdamage due to a sequence of compressive and torsional damaging loads. The mean decrease in Young's modulus was over four times greater than that in the shear modulus after the compressive overload, while there was no difference between the decrease in the axial and torsional stiffnesses after the torsional overload. The total microcrack density due to compression was uniform across the radius of the cylindrical specimens, while the mean density of microcracks due to torsional overloading increased from the axis of the cylindrical specimen to the circumference. The high density of microcracks near the axis of the specimen following torsional overloading was unexpected because of the low strains. Nearly 40% of the microcracks due to torsion propagated from pre-existing microcracks caused by axial compression, indicating that existing microcracks may extend at relatively low strain if the loading mode changes. The propagating microcracks were, on average, longer than the initiating microcracks due to either compressive or torsional loading. Damage due to axial compression appears to increase the susceptibility of trabecular bone to damage propagation during subsequent torsional loads, but it has little effect on the elastic properties in shear.     

Feasibility of using a magnetic tracking device for measuring carpal kinematics

While several different methods have been used to measure carpal kinematics, biplanar radiography is generally considered to be the most accurate and popular one. However, biplanar radiography is tedious and so only pseudo-dynamic kinematics can be measured. Recently, magnetic tracking system has been developed for the measurement of joint kinematics which is versatile and easy to use and so the possibility of measuring motions dynamically. In this study, the capability of a magnetic tracking device to accurately measure carpal kinematics was investigated by comparing it with biplanar radiography. The kinematics of the third metacarpal, scaphoid, and lunate in five fresh cadaveric specimens were measured using both methods as the wrists were placed in eight positions. The finite screw rotation of each bone with respect to the distal radius during selecting the seven wrist motions was calculated for both measuring techniques and compared. In general, the kinematics for all three bones measured by using either magnetic tracking device or biplanar radiography was identical and showed no statistical difference. The averaged differences ranged from 0.0 to 2.0°. These differences were due to the potential effect of the weight of the sensors and the interference of the attaching rod to the surrounding tissue. It is concluded that the application of the magnetic tracking device to carpal kinematics is warranted, if proper technical procedures as suggested are followed.