Two different correlations between nanoindentation modulus and mineral content in the bone-cartilage interface

The biomechanical properties of the zone of calcified cartilage (ZCC) in articulating joints are of clinical relevance due to the role ZCC plays in load transfer from cartilage to bone. To determine the micron-level mechanical properties and their correlation to mineral concentration in the ZCC, we combined nanoindentation (for micrometer level stiffness E(r) and hardness H) and quantitative back-scattered electron imaging or qBEI (for micrometer level mean calcium concentration Ca(Mean)) to study the ZCC-subchondral bone junction in 3 embedded human patellae. Nanoindentation line scans were correlated to qBEI analysis in the ZCC. The correlation between local stiffness and local mineral content was different in calcified cartilage compared to bone. The stiffness and hardness of calcified cartilage was typically lower than subchondral bone for the same mineral content. ZCC showed a wider range of variation in calcium content (1-28 wt %) compared to subchondral bone (16-26 wt %). 2D material property maps of the ZCC were generated from the mechanical-mineral correlation, showing that bands of high and low stiffness were found between the bone and tidemark, and between the ZCC and the unmineralized cartilage.     

The effect of methylation of phosphatidylethanolamine on the behaviour of lipid monolayers at the air-water interface

Monolayers of DPPE and its N-methylated derivatives including DPPC have been investigated at 23 and 37 degrees C using a modified Langmuir-Wilhelmy surface balance. The monolayers have been subjected to dynamic compression and expansion, and some characteristics of the surfaces have been determined. The minimum surface tension attained by surfaces containing the lipids (maximum surface pressures sustained by the films) depended on the extent of methylation of the head group. Monolayers of DPPE or N-MeDPPE collapsed at surface tensions of 12-16 mN.m-1, whereas those containing N,N-diMeDPPE and DPPC could be compressed to near zero surface tension. The areas per molecule occupied by these lipids under high compression varied slightly and not systematically with head-group methylation. Monolayers containing mixtures of DPPC and DPPE were also studied under the same conditions. The monolayers showed some deviation from the behaviour expected if they were to have characteristics of ideally mixed systems. The minimum surface tensions attained suggested that monolayers containing 50 mol% or more DPPC might be further enriched during compression by some selective exclusion of the DPPE. At high surface pressures, some positive deviations in nominal areas per molecule from that expected for ideal mixing were observed in the monolayers made with 50 mol% or more DPPC. These deviations might be caused by packing disruptions associated with the explosion of lipid from the films.     

The effect of sweet stimuli on oral behaviour in the chicken

The oral behaviour of the chicken was investigated in responseto a variety of concentrations of fructose, sucrose and carboxymethylcellulosesolutions. Both fructose and sucrose produced a similar increasein beak and tongue movements whereas an equivalent increasewas only elicited by carboxymethylcellulose at much higher viscosities.An increase in head shaking behaviour only occurred when thebirds were stimulated with sucrose solutions. Increases in beakwiping behaviour occurred only with sucrose and carboxymethylcellulosesolutions. It was concluded that no single characteristic ofthe stimulus chemical was responsible for all the differentbehaviours shown.     

The effect of stimuli that isolate S-cones on early saccades and the gap effect

Disappearance of the fixation spot before the appearance of a peripheral target typically reduces average saccadic reaction times (the gap effect) and may also produce a separate population of early or express saccades. The superior colliculus (SC) is generally believed to be critically involved in generating both effects. As the direct sensory input to the SC does not encode colour information, to determine whether this input was critical in generating the gap effect or express saccades we used coloured targets which this pathway cannot distinguish. Our observers still made early saccades to colour-defined targets, but these were anticipations in response to the offset of the non-coloured fixation target. We also show that a gap effect still occurs when either the fixation target or the peripheral target is colour defined, suggesting that direct sensory input to the SC is not required and that information about the location of colour-defined targets is abstracted prior to processing within the SC.     

Comparison of biophysical stimuli for mechano-regulation of tissue differentiation during fracture healing

Most long-bone fractures heal through indirect or secondary fracture healing, a complex process in which endochondral ossification is an essential part and bone is regenerated by tissue differentiation. This process is sensitive to the mechanical environment, and several authors have proposed mechano-regulation algorithms to describe it using strain, pore pressure and/or interstitial fluid velocity as biofeedback variables. The aim of this study was to compare various mechano-regulation algorithms' abilities to describe normal fracture healing in one computational model. Additionally, we hypothesized that tissue differentiation during normal fracture healing could be equally well regulated by the individual mechanical stimuli, e.g. deviatoric strain, pore pressure or fluid velocity. A biphasic finite element model of an ovine tibia with a 3mm fracture gap and callus was used to simulate the course of tissue differentiation during normal fracture healing. The load applied was regulated in a biofeedback loop, where the load magnitude was determined by the interfragmentary movement in the fracture gap. All the previously published mechano-regulation algorithms studied, simulated the course of normal fracture healing correctly. They predicted (1) intramembranous bone formation along the periosteum and callus tip, (2) endochondral ossification within the external callus and cortical gap, and (3) creeping substitution of bone towards the gap from the initial lateral osseous bridge. Some differences between the effects of the algorithms were seen, but they were not significant. None of the volumetric components, i.e. pore pressure or fluid velocity, alone were able to correctly predict spatial or temporal tissue distribution during fracture healing. However, simulation as a function of only deviatoric strain accurately predicted the course of normal fracture healing. This suggests that the deviatoric component may be the most significant mechanical parameter to guide tissue differentiation during indirect fracture healing.     

The functions of autophagy at the tumour-immune interface

Autophagy is frequently induced in the hypoxic tumour microenvironment. Accumulating evidence reveals important functions of autophagy at the tumour-immune interface. Herein, we propose an update on the roles of autophagy in modulating tumour immunity. Autophagy promotes adaptive resistance of established tumours to the cytotoxic effects of natural killer cells (NKs), macrophages and effector T cells. Increased autophagic flux in tumours dampen their immunogenicity and inhibits the expansion of cytotoxic T lymphocytes (CTLs) by suppressing the activation of STING type I interferon signalling (IFN-I) innate immune sensing pathway. Autophagy in suppressive tumour-infiltrating immune subsets maintains their survival through metabolic remodelling. On the other hand, autophagy is involved in the antigen processing and presentation process, which is essential for anti-tumour immune responses. Genetic deletion of autophagy induces spontaneous tumours in some models. Thus, the role of autophagy is context-dependent. In summary, our review has revealed the dichotomous roles of autophagy in modulating tumour immunity. Broad targeting of autophagy may not yield maximal benefits. The characterization of specific genes regulating tumour immunogenicity and innovation in targeted delivery of autophagy inhibitors into certain tumours are among the most urgent tasks to sensitize cold cancers to immunotherapy.     

The effect of external stimuli on the attack readiness of a cichlid fish

Summary The readiness of a cichlid fish to attack conspecifics, measured by the number of attacks it delivers per minute in a standardized situation, can immediately be increased by presenting another fish or a dummy of a fish for a short time. After that the attack readiness returns exponentially to its previous level. The analysis of the immediate increase in the attack readiness has shown that the appearance of a dummy causes an additive increase in attack readiness, which is raised by a constant amount after the dummy presentation.

---

Zusammenfassung Die Bereitschaft eines Cichliden, Artgenossen anzugreifen, gemessen an der Zahl der Angriffe, die das Tier pro Minute in einer standardisierten Situation liefert, kann augenblicklich durch die kurzzeitige Darbietung eines weiteren Fisches oder einer entsprechenden Attrappe gesteigert werden. Danach kehrt die Angriffsbereitschaft exponentiell auf ihr früheres Niveau zurück. Die Untersuchung der augenblicklichen Steigerung der Angriffsbereitschaft hat gezeigt, daß das Erscheinen einer Attrappe die Bereitschaft additiv um einen konstanten Betrag erhöht.

     

The effect of the interface on the bone stresses beneath tibial components

It was proposed that the stresses in the layer of bone immediately beneath a tibial component are an important determinant of fixation durability. Using finite element analysis, (ANSYS), the stresses were determined as a function of the amount of bone resection, the localization or completeness of implant-bone contact, and the interface material. The model was of two-dimensional sagittal slices consisting of quadrilateral elements (1 mm) with a range of seventeen material properties determined by CT scans. Typical prosthesis designs shifted the center of pressure more centrally rather than posteriorly, and thus increased anterior bone stresses. Resection up to 10 mm could actually decrease bone stresses due to an increase in bone surface area as long as complete coverage was obtained. A cement interface or direct metal on bone produced identical stresses. However a 1 mm complian: interface significantly reduced stresses in regions of high elastic modulus gradient. For rigid interfaces, the contact can be irregular, which leads to areas of over and understressing of bone. These conclusions have implications related to implant design.     

Analogies to demonstrate the effect of roughness on surface wettability

This article presents an analogy to illustrate the effect of surface roughness on surface wettability. I used a water-filled balloon to represent water droplet, a toothpick to represent surface roughness and Styrofoam as the surface. The analogies presented in this article will help visualize how roughness affects the wettability of the surface and therefore can be used to introduce surface wettability to high school students.     

Predicting the effect of steroids on membrane biophysical properties based on the molecular structure

The relationship between sterol structure and the resulting effects on membrane physical properties is still unclear, owing to the conflicting results found in the current literature. This study presents a multivariate analysis describing the physical properties of 83 steroid membranes. This first structure-activity analysis supports the generally accepted physical effects of sterols in lipid bilayers. The sterol chemical substituents and the sterol/phospholipid membrane physical properties were encoded by defining binary variables for the presence/absence of those chemical substituents in the polycyclic ring system and physical parameters obtained from phospholipid mixtures containing those sterols. Utilizing Principal Coordinates Analysis, the steroid population was grouped into five well-defined clusters according to their chemical structures. An examination of the membrane activity of each sterol structural cluster revealed that a hydroxyl group at C3 and an 8-10 carbon isoalkyl side-chain at C17 are mainly present in membrane active sterols having rigidifying, molecular ordering/condensing effects and/or a raft promoting ability. In contrast, sterol chemical structures containing a keto group at C3, a C4-C5-double bond, and polar groups or a short alkyl side-chain at C17 (3 to 7 atoms) are mostly found in sterols having opposite effects. Using combined multivariate approaches, it was concluded that the most important structural determinants influencing the physical properties of sterol-containing mixtures were the presence of an 8-10 carbon C17 isoalkyl side-chain, followed by a hydroxyl group at C3 and a C5-C6 double bond. Finally, a simple Logistic Regression model predicting the dependence of membrane activity on sterol chemical structure is proposed.     

Pectin-lipid assembly at the air-water interface: effect of the pectin charge distribution

Pectins are anionic polysaccharides that are sensitive to cations, a property that is widely used in food science. The interactions of a cationic lipid film (dimethyldioctadecylammonium bromide, DODAB) with a set of pectins bearing the same charge, which was either distributed randomly or pseudorandomly or blockwise, are investigated. The combination of Brewster angle microscopy BAM and infrared reflection-absorption spectroscopy IRRAS at the air-water interface reveals that pectin strongly binds to the cationic lipid film in forming a stacked layer underneath the lipid film. The detailed vibrational study of this stable mixed film indicates furthermore that pectin induces a disorder in the internal structure of the cationic film. The strong binding induces a splitting of the carboxylate stretching mode of pectin that is pressure and charge distribution dependent. The occurrence of an intermediate plateau below the collapse of the mixed film originates probably from a change in conformation of the pectin structure underneath the film.     

Phosphorylation at the interface

Proteomic studies have identified thousands of eukaryotic phosphorylation sites (phosphosites), but few are functionally characterized. Nishi et?al., in this issue of Structure, characterize phosphosites at protein-protein interfaces and estimate the effect of their phosphorylation on interaction affinity, by combining proteomics data with protein structures.     

The effect of external stimuli on movement of Asterias amurensis starfish]

Studies have been made on local and total motor reactions of the starfish to stimuli of different modalities. It is suggested that differences in the pattern of papillae excitation and those in total reactions to salt, mechanical stimulation and changes in the intensity of illumination are associated with structural and functional heterogeneity of receptors and afferent pathways in the lower regular layer of the nervous plexus. The ability of segment motoneurons to change the direction of tube feet movement in absence of influences from the nervous ring was demonstrated. Possible scheme of control of pedicellar movement evoked by external stimulation is discussed.     

Headshaking in fowls: The effect of environmental stimuli

The incidence of headshaking in domestic fowls (Gallus domesticus) is influenced by both social and environmental factors; it was more frequent in larger groups and in subordinate birds, and it could be greatly increased by exposure to disturbing stimuli. The findings are not readily explained by earlier suggestions that it is a response to frustration of movement, that it serves to increase sensory input under conditions of social isolation in barren surroundings, or that it is a displacement reaction to conflict situations. Evidence is presented to show that it occurred in contexts demanding increased attention, for example, upon the presentation of novel or disturbing stimuli, and it is proposed that headshaking is an “alerting response”.     

Mixed-mode failure strength of implant-cement interface specimens with varying surface roughness

Aseptic loosening at the implant-cement interface is a well-documented cause of failure in joint arthroplasty. Traditionally, the strength of the implant-cement interface is determined using uni-axial normal and shear loading tests. However, during functional loading, the implant fixation sites are loaded under more complex stress conditions. For this purpose, the strength of the implant-cement interface under mixed-mode tensile and shear loading conditions was determined in this study using interface specimens with varying interface roughness. For the lowest roughness value analyzed (R(a)=0.89 μm), the interface strength was 0.40-1.95 MPa at loading angles varying between pure tension and shear, whereas this was 4.90-9.90 MPa for the highest roughness value (R(a)=2.76 μm). The interface strength during pure shear (1.95-9.90 MPa) was substantially higher than during pure tension (0.58-6.67 MPa). Polynomial regression was used to fit a second-order interpolation function through the experimental interface strength data (R2=0.85; p<0.001), relating the interface strength (S [MPa]) to the interface loading angle (α [degrees]) and interface roughness (R(a) [μm]): S(α,R(a))=0.891R2(a)+0.001α2-0.189R(a)-0.064α-0.060. Finally, an interface failure criterion was derived from the interface strength measurements, describing the risk of failure at the implant-cement interface when subjected to a certain tensile and shear stress using only the interface strength in pure tensile and shear direction. The findings presented in this paper can be used in numerical models to simulate loosening at the implant-cement interface.