Ion induced deformation of soft tissue

In this paper the effects of changing the ion concentration in and around a sample of soft tissue are investigated. The triphasic theory developed by Laiet al. (1990,Biomechanics of Diarthrodial Joints, Vol. 1, Berlin, Springer-Verlag) is reduced to two coupled partial differential equations involving fluid ion concentration and tissue solid deformation. These equations are given in general form for Cartesian, cylindrical and spherical geometries. After solving the two equations quantities such as fluid velocity, fluid pressure, chemical potentials and chemical expansion stress may be easily calculated. In the Cartesian geometry comparison is made with the experimental and theoretical work of Myerset al. (1984,ASME J. biomech. Engng,106, 151–158). This dealt with changing the ion concentration of a salt shower on a strip of bovine articular cartilage. Results were obtained in both free swelling and isometric tension states, using an empirical formula to acount for ion induced deformation. The present theory predicts lower ion concentrations inside the tissue than this earlier work. A spherical sample of tissue subjected to a change in salt bath ion concentration is also considered. Numerical results are obtained for both hypertonic and hypotonic bathing solutions. Of particular interest is the finding that tissue may contract internally before reaching a final swollen equilibrium state or swell internally before finally contracting. By considering the relative magnitude, and also variation throughout the time course of terms in the governing equations, an even simpler system is deduced. As well as being linear the concentration equation in the new system is uncoupled. Results obtained from the linear system compare well with those from the spherical section. Thus, biological swelling situations may be modelled by a simple system of equations with the possibility, of approximate analytic solutions in certain cases.     

The unstirred layer during osmotic flow into a tubule

The interaction between osmotic inflow through the wall of a narrow tubule and bulk flow in the tubule is described. Solution are found by a finite difference method, and two approximate analytic solutions are given. Results given here enable more accurate estimates of osmotic permeability to be obtained for the tubule wall. The theory predicts the behaviour of unstirred layers as experimental parameters are varied and enables tubule experiments to be designed so as to reduce unwanted unstirred layer effects.     

The Caenorhabditis elegans gene, gly-2, can rescue the N-acetylglucosaminyltransferase V mutation of Lec4 cells

UDP-N-acetylglucosamine:alpha-6-d-mannoside beta-1,6-N-acetylglucosaminyltransferase V (GlcNAc-TV) is a regulator of polylactosamine-containing N-glycans and is causally involved in T cell regulation and tumor metastasis. The Caenorhabditis elegans genome contains a single orthologous gene, gly-2, that is transcribed and encodes a 669-residue type II membrane protein that is 36.7% identical to mammalian GlcNAc-TV (Mgat-5). Recombinant GLY-2 possessed GlcNAc-TV activity when assayed in vitro, and protein truncations demonstrated that the N-terminal boundary of the catalytic domain is Ile-138. gly-2 complemented the Phaseolus vulgaris leucoagglutinin binding defect of Chinese hamster ovary Lec4 cells, whereas GLY-2(L116R), an equivalent mutation to that which causes the Lec4A phenotype, could not. We conclude that the worm gene is functionally interchangeable with the mammalian form. GlcNAc-TV activity was detected in wild-type animals but not those homozygous for a deletion allele of gly-2. Activity was restored in mutant animals by an extrachromosomal array that encompassed the gly-2 gene. Green fluorescent protein reporter transgenes driven by the gly-2 promoter were expressed by developing embryos from the late comma stage onward, present in a complex subset of neurons in larvae and, in addition, the spermathecal and pharyngeal-intestinal valves and certain vulval cells of adults. However, no overt phenotypes were observed in animals homozygous for deletion alleles of gly-2.     

UNC-5 function requires phosphorylation of cytoplasmic tyrosine 482, but its UNC-40-independent functions also require a region between the ZU-5 and death domains

Members of the UNC-5 protein family are transmembrane receptors for UNC-6/netrin guidance cues. To analyze the functional roles of different UNC-5 domains, we sequenced mutations in seven severe and three weak alleles of unc-5 in Caenorhabditis elegans. Four severe alleles contain nonsense mutations. Two weak alleles are truncations of the cytodomain, but one is a missense mutation in an extracellular immunoglobulin domain. To survey the function of different regions of UNC-5, wild-type and mutant unc-5::HA transgenes were tested for their ability to rescue the unc-5(e53) null mutant. Our data reveal partial functional requirements for the extracellular domains and identify a portion of the cytoplasmic juxtamembrane (JM) region as essential for rescue of migrations. When nine cytodomain tyrosines, including seven in the JM region, are mutated to phenylalanine, UNC-5 function and tyrosine phosphorylation are largely compromised. When F482 in the JM region of the mutant protein is reverted to tyrosine, UNC-5 tyrosine phosphorylation and in vivo function are largely recovered, suggesting that Y482 phosphorylation is critical to UNC-5 function in vivo. Our data also show that part of the ZU-5 motif is required for UNC-40-independent signaling of UNC-5.     

Controlling emerging infectious diseases like SARS

To control emerging infectious diseases like SARS, it is necessary to resort to basic control measures that limit exposures to infectious individuals. These measures include isolating cases at diagnosis, quarantining household members and tracing contacts of diagnosed cases, providing the community with advice on how to reduce exposures, and closing schools. To justify such intervention it is important to understand how well each of these measures helps to limit transmission. In this paper, we determine the effect of a number of different interventions on the effective reproduction number and estimate requirements to achieve elimination of the infectious disease. We find that the strategy of tracing and quarantining contacts of diagnosed cases can be very successful in reducing transmission.     

Comparison of models for flow induced deformation of soft biological tissue

The behaviour of a deformable porous medium during the flow of fluid under a pressure difference is examined for both infinitesimal and finite deformations. Models for both cases are solved for the problem of steady one-dimensional compression and compared with experimental data from Parker et al. (J. appl. Mech. 54, 794-800, 1987) for a polyurethane sponge. The purpose of this study is to identify a simple model which agrees qualitatively with these published results. To relate the stress relations for biological tissues to the data for polymer sponges (Parker et al., 1987) a translation of 1.1 kPa was introduced. This allows for some structural differences between the two media. It was found that the infinitesimal models were adequate up to 20% strain, but significant divergence occurred for higher strains. A finite deformation model with the permeability depending exponentially on the strain gave the most consistent results and required the fitting of only two parameters.