Reading Out Olfactory Receptors: Feedforward Circuits Detect Odors in Mixtures without Demixing.

The olfactory system, like other sensory systems, can detect specific stimuli of interest amidst complex, varying backgrounds. To gain insight into the neural mechanisms underlying this ability, we imaged responses of mouse olfactory bulb glomeruli to mixtures. We used this data to build a model of mixture responses that incorporated nonlinear interactions and trial-to-trial variability and explored potential decoding mechanisms that can mimic mouse performance when given glomerular responses as input. We find that a linear decoder with sparse weights could match mouse performance using just a small subset of the glomeruli (∼15). However, when such a decoder is trained only with single odors, it generalizes poorly to mixture stimuli due to nonlinear mixture responses. We show that mice similarly fail to generalize, suggesting that they learn this segregation task discriminatively by adjusting task-specific decision boundaries without taking advantage of a demixed representation of odors.

An odor interaction model of binary odorant mixtures by a partial differential equation method.

A novel odor interaction model was proposed for binary mixtures of benzene and substituted benzenes by a partial differential equation (PDE) method. Based on the measurement method (tangent-intercept method) of partial molar volume, original parameters of corresponding formulas were reasonably displaced by perceptual measures. By these substitutions, it was possible to relate a mixture's odor intensity to the individual odorant's relative odor activity value (OAV). Several binary mixtures of benzene and substituted benzenes were respectively tested to establish the PDE models. The obtained results showed that the PDE model provided an easily interpretable method relating individual components to their joint odor intensity. Besides, both predictive performance and feasibility of the PDE model were proved well through a series of odor intensity matching tests. If combining the PDE model with portable gas detectors or on-line monitoring systems, olfactory evaluation of odor intensity will be achieved by instruments instead of odor assessors. Many disadvantages (e.g., expense on a fixed number of odor assessors) also will be successfully avoided. Thus, the PDE model is predicted to be helpful to the monitoring and management of odor pollutions.

Dynamic mixtures: challenges and opportunities for the amplification and sensing of scents.

Nature generates compounds as complicated mixtures, but surprisingly little is known about the synergies or inhibitory effects of compound mixtures, which is likely to become an important research area in life sciences in the near future. Some recently developed concepts in dynamic combinatorial/covalent chemistry (DCC) have been applied to amplify (increase the intensity and long-lastingness of perception) and sense (selectively detect and discriminate) individual bioactive volatile molecules in compound mixtures. This Concept article focuses on the potential of DCC to impact and modulate the biological and chemical properties of mixtures of bioactive volatile compounds to gain a more fundamental understanding of the properties of compound mixtures in molecular recognition.

Sarcoptes scabiei (Acari: Sarcoptidae) mite extract modulates expression of cytokines and adhesion molecules by human dermal microvascular endothelial cells.

The inflammatory and immune responses seen with the worldwide disease scabies, caused by the mite Sarcoptes scabiei (De Geer) (Acari: Sarcoptidae), are complex. Clinical symptoms are delayed for weeks in patients when they are infested with scabies for the first time. This study was undertaken to elucidate the role of the human dermal microvascular endothelial cell (HMVEC-D) in modulating the inflammatory and immune responses in the skin to S. scabiei. Extracts of S. scabiei were incubated with HMVEC-D and the expression of adhesion molecules and chemokine receptors on the cells and the secretion of selected cytokines were determined by enzyme-linked immunosorbent assay. S. scabiei extract was found to inhibit HMVEC-D expression of E-selectin and vascular cell adhesion molecule-1, although not intercellular adhesion molecule-1. The secretion of interleukin-8 also was inhibited by S. scabiei extract. S. scabiei extract increased expression of the chemokine receptor CXCR-1 and both down-regulated and up-regulated expression of CXCR-2, depending on the concentration tested. These findings help explain the delayed inflammatory reaction to infestation with S. scabiei.

The correspondence between equilibrium biphasic and triphasic material properties in mixture models of articular cartilage.

Mixture models have been successfully used to describe the response of articular cartilage to various loading conditions. Mow et al. (J. Biomech. Eng. 102 (1980) 73) formulated a biphasic mixture model of articular cartilage where the collagen-proteoglycan matrix is modeled as an intrinsically incompressible porous-permeable solid matrix, and the interstitial fluid is modeled as an incompressible fluid. Lai et al. (J. Biomech. Eng. 113 (1991) 245) proposed a triphasic model of articular cartilage as an extension of their biphasic theory, where negatively charged proteoglycans are modeled to be fixed to the solid matrix, and monovalent ions in the interstitial fluid are modeled as additional fluid phases. Since both models co-exist in the cartilage literature, it is useful to show how the measured properties of articular cartilage (the confined and unconfined compressive and tensile moduli, the compressive and tensile Poisson's ratios, and the shear modulus) relate to both theories. In this study, closed-form expressions are presented that relate biphasic and triphasic material properties in tension, compression and shear. These expressions are then compared to experimental findings in the literature to provide greater insight into the measured properties of articular cartilage as a function of bathing solutions salt concentrations and proteoglycan fixed-charge density.

A method to estimate the elastic properties of the extracellular matrix of articular cartilage.

In this work we propose a method to estimate the elastic properties of the extracellular matrix of articular cartilage, once the elastic properties of the chondrocytes and the whole tissue are known. The influence of the elastic properties of the tissue and the cell concentration on the estimated elastic properties of the matrix are investigated.

A nonlinear hyperelastic mixture theory model for anisotropy, transport, and swelling of annulus fibrosus.

A precise knowledge of the local mechanical and chemical environment around the nerve endings and disc cells in the annulus fibrosus will shed insight on understanding the mechanism of low-back pain and disc degeneration. It would also present an effective tool for the studies of the intervertebral disc structure-function relationship and provide guidance to disc tissue engineering. Experimental difficulties preclude the direct and simultaneous measurement of many of the important physical quantities, such as annulus pressurization, nutrient and electrolyte transport, and mechanical and swelling deformation. Considering that many of these quantities are coupled and that the annulus is highly anisotropic, interpretation of the results would be extremely challenging without an appropriate theoretical framework. In this study, we develop a nonlinear hyperelastic fiber-reinforced continuum mixture theory model for the annulus fibrosus. Special attention is given to the anisotropic nature of the annulus. On the basis of the lamella structure of annulus, and derived from a Helmholtz energy function, a locally transversely isotropic stress-strain relation is adopted for explicit representation of the collagen fiber orientations in general finite deformation situation. The exponential form of the Helmholtz energy function naturally reduces to the infinitesimal deformation form, and the equivalence between the current model coefficients and engineering elastic constants is established under the infinitesimal deformation. This model is able to describe the anisotropic finite and infinitesimal deformation, tension-compression nonlinearity, osmotic swelling, pressurization, electrical potential and current, and water and ion transports as well as the electroneutral nutrient (or growth factor) transport within the annulus.

Changes in the refractive index of the stroma and its extrafibrillar matrix when the cornea swells.

The transparency of the corneal stroma is critically dependent on the hydration of the tissue; if the cornea swells, light scattering increases. Although this scattering has been ascribed to the disruption caused to the arrangement of the collagen fibrils, theory predicts that light scattering could increase if there is an increased mismatch in the refractive indices of the collagen fibrils and the material between them. The purpose of this article is to use Gladstone and Dale's law of mixtures to calculate volume fractions for a number of different constituents in the stroma, and use these to show how the refractive indices of the stroma and its constituent extrafibrillar material would be expected to change as more solvent enters the tissue. Our calculations predict that solvent entering the extrafibrillar space causes a reduction in its refractive index, and hence a reduction in the overall refractive index of the bovine stroma according to the equation n'(s) = 1.335 + 0.04/(0.22 + 0.24 H'), where n'(s) is the refractive index and H' is the hydration of the swollen stroma. This expression is in reasonable agreement with our experimental measurements of refractive index versus hydration in bovine corneas. When the hydration of the stroma increases from H = 3.2 to H = 8.0, we predict that the ratio of the refractive index of the collagen fibrils to that of the material between them increases from 1.041 to 1.052. This change would be expected to make only a small contribution to the large increase in light scattering observed when the cornea swells to H = 8.